期刊文献+
共找到4,001篇文章
< 1 2 201 >
每页显示 20 50 100
Potential therapeutic molecular targets for blood-brain barrier disruption after subarachnoid hemorrhage 预览
1
作者 Hideki Kanamaru Hidenori Suzuki 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第7期1138-1143,共6页
Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities.Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial ... Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities.Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial pressure,followed by global cerebral ischemia.Post-subarachnoid hemorrhage ischemia,tissue injuries as well as extravasated blood components and the breakdown products activate microglia,astrocytes and Toll-like receptor 4,and disrupt blood-brain barrier associated with the induction of many inflammatory and other cascades.Once blood-brain barrier is disrupted,brain tissues are directly exposed to harmful blood contents and immune cells,which aggravate brain injuries furthermore.Blood-brain barrier disruption after subarachnoid hemorrhage may be developed by a variety of mechanisms including endothelial cell apoptosis and disruption of tight junction proteins.Many molecules and pathways have been reported to disrupt the blood-brain barrier after subarachnoid hemorrhage,but the exact mechanisms remain unclear.Multiple independent and/or interconnected signaling pathways may be involved in blood-brain barrier disruption after subarachnoid hemorrhage.This review provides recent understandings of the mechanisms and the potential therapeutic targets of blood-brain barrier disruption after subarachnoid hemorrhage. 展开更多
关键词 blood-brain barrier early brain injury ENDOTHELIAL cell SUBARACHNOID HEMORRHAGE TIGHT junction inflammation matricellular protein TOLL-LIKE receptor 4 TLR4
在线阅读 下载PDF
Intermedin in Paraventricular Nucleus Attenuates Sympathoexcitation and Decreases TLR4-Mediated Sympathetic Activation via Adrenomedullin Receptors in Rats with Obesity-Related Hypertension
2
作者 Jing Sun Xing-Sheng Ren +5 位作者 Ying Kang Hang-Bing Dai Lei Ding Ning Tong Guo-Qing Zhu Ye-Bo Zhou 《神经科学通报:英文版》 SCIE CAS CSCD 2019年第1期34-46,共13页
Intermedin/adrenomedullin-2(IMD/AM2), a member of the calcitonin gene-related peptide/AM family,plays an important role in protecting the cardiovascular system. However, its role in the enhanced sympathoexcitation in ... Intermedin/adrenomedullin-2(IMD/AM2), a member of the calcitonin gene-related peptide/AM family,plays an important role in protecting the cardiovascular system. However, its role in the enhanced sympathoexcitation in obesity-related hypertension is unknown. In this study, we investigated the effects of IMD in the paraventricular nucleus(PVN) of the hypothalamus on sympathetic nerve activity(SNA), and lipopolysaccharide(LPS)-induced sympathetic activation in obesity-related hypertensive(OH)rats induced by a high-fat diet for 12 weeks. Acute experiments were performed under anesthesia. The dynamic alterations of sympathetic outflow were evaluated as changes in renal SNA and mean arterial pressure(MAP) in response to specific drugs. Male rats were fed a control diet(12% kcal as fat) or a high-fat diet(42% kcal as fat) for 12 weeks to induce OH. The results showed that IMD protein in the PVN was downregulated, but Toll-like receptor 4(TLR4) and plasma norepinephrine(NE, indicating sympathetic hyperactivity) levels, and systolic blood pressure were increased in OH rats. LPS(0.5 lg/50 nL)-induced enhancement of renal SNA and MAP was greater in OH rats than in obese or control rats. Bilateral PVN microinjection of IMD(50 pmol)caused greater decreases in renal SNA and MAP in OH rats than in control rats, and inhibited LPS-induced sympatheticactivation, and these were effectively prevented in OH rats by pretreatment with the AM receptor antagonist AM22-52.The mitogen-activated protein kinase/extracellular signalregulated kinase(ERK) inhibitor U0126 in the PVN partially reversed the LPS-induced enhancement of SNA. However,IMD in the PVN decreased the LPS-induced ERK activation,which was also effectively prevented by AM22-52. Chronic IMD administration resulted in significant reductions in the plasma NE level and blood pressure in OH rats. Moreover,IMD lowered the TLR4 protein expression and ERK activation in the PVN, and decreased the LPS-induced sympathetic overactivity. These results indicate that IMD in the PVN attenuat 展开更多
关键词 INTERMEDIN Sympathoexcitation Obesityrelated HYPERTENSION PARAVENTRICULAR NUCLEUS TOLL-LIKE receptor 4
Gut microbial dysbiosis associates hepatocellular carcinoma via the gut-liver axis 预览
3
作者 Jian-Wen Jiang Xin-Hua Chen +1 位作者 Zhigang Ren Shu-Sen Zheng 《国际肝胆胰疾病杂志:英文版》 SCIE CAS CSCD 2019年第1期19-27,共9页
Background:Hepatocellular carcinoma(HCC)is one of the most common malignancies in the world.Gut microbiota has been demonstrated to play a critical role in liver inflammation,chronic fibrosis,liver cirrhosis,and HCC d... Background:Hepatocellular carcinoma(HCC)is one of the most common malignancies in the world.Gut microbiota has been demonstrated to play a critical role in liver inflammation,chronic fibrosis,liver cirrhosis,and HCC development through the gut-liver axis.Data sources:Recently there have been several innovative studies investigating gut microbial dysbiosismediated enhancement of HCC through the gut-liver axis.Literatures from January 1998 to January 2018 were searched in the PubMed database using the keywords“gut microbiota”and“hepatocellular carcinoma”or“liver cancer”,and the results of experimental and clinical studies were analyzed.Results:Gut microbial dysbiosis accompanies the progression of alcoholic liver disease,non-alcoholic fatty liver disease and liver cirrhosis,and promotes HCC progression in an experimental mouse model.The immune system and key factors such as Toll-like receptor 4 are involved in the process.There is evidence for gut microbial dysbiosis in hepatitis virus-related HCC patients.Conclusions:Gut microbial dysbiosis is closely associated with hepatic inflammation disease and HCC through the gut-liver axis.With the enhanced understanding of the interactions between gut microbiota and liver through the gut-liver axis,new treatment strategies for HCC are being developed. 展开更多
关键词 Gut-liver AXIS GUT microbiota Hepatocellular carcinoma Lipopolysaccharide TOLL-LIKE receptor 4
在线阅读 下载PDF
Effect of Soothing Gan(Liver) and Invigorating Pi(Spleen) Recipes on TLR4-p38 MAPK Pathway in Kupffer Cells of Non-alcoholic Steatohepatitis Rats
4
作者 GONG Xiang-wen XU Yong-jian +4 位作者 YANG Qin-he LIANG Yin-ji ZHANG Yu-pei WANG Guan-long LI Yuan-yuan 《中国结合医学杂志:英文版》 SCIE CAS CSCD 2019年第3期216-224,共9页
Objective: To investigate the mechanism of inflammatory-mediated toll-like receptor 4(TLR4)-p38 mitogen-activated protein kinase(p38 MAPK) pathway in Kupffer cells(KCs) of non-alcoholic steatohepatitis(NASH) rats and ... Objective: To investigate the mechanism of inflammatory-mediated toll-like receptor 4(TLR4)-p38 mitogen-activated protein kinase(p38 MAPK) pathway in Kupffer cells(KCs) of non-alcoholic steatohepatitis(NASH) rats and the intervention effect of soothing Gan(Liver) and invigorating Pi(Spleen) recipes on this pathway. Methods: After 1 week of acclimatization, 120 Sprague-Dawley male rats were randomly divided into 8 groups using a random number table(n=15 per group): normal group, model group, low-dose Chaihu Shugan Powder(柴胡疏肝散, CHSG) group(3.2 g/kg), high-dose CHSG group(9.6 g/kg), low-dose Shenling Baizhu Powder(参苓白术散, SLBZ) group(10 g/kg), high-dose SLBZ(30 g/kg) group, and low-and highdose integrated recipe(L-IR, H-IR) groups. All rats in the model and treatment groups were fed with a high-fat diet(HFD). The treatments were administrated by gastrogavage once daily and lasted for 26 weeks. The liver tissues were detected with hematoxylin-eosin(HE) and oil red O staining. Levels of liver lipids, serum lipids and transaminases were measured. KCs were isolated from the livers of rats to evaluate the mRNA expressions of TLR4 and p38 MAPK by real-time fluorescence quantitative polymerase chain reaction, and proteins expressions of TLR4, p-p38 MAPK and p38 MAPK by Western blot. Levels of inflammatory cytokines including tumor necrosis factor α(TNF-α), interleukin(IL)-1 and IL-6 in KCs were measured by enzyme-linked immunosorbent assay. Results: After 26 weeks of HFD feeding, HE and oil red O staining showed that the NASH model rats successfully reproduced typical pathogenesis and histopathological features. Compared with the normal group, the model group exhibited significant increases in body weight, liver weight, liver index, serum levels of total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol, and aspartate aminotransferase as well as TC and TG levels in liver tissues, and significant decrease in serum level of high-density lipoprotein cholesterol(P<0.05 or P<0.01), whi 展开更多
关键词 non-alcoholic steatohepatitis soothing GAN (Liver)and invigorating PI (Spleen)recipes Kupffer cel toll-like receptor 4-p38 MITOGEN-ACTIVATED protein kinase signaling pathway inflammation Chinese medicine
Protective Effects and Mechanisms of Shenhua Tablet (肾华片)on Toll-Like Receptors in Rat Model of Renal Ischemia-Reperfusion Injury
5
作者 LI Qing-ping WEI Ri-bao +5 位作者 YANG Xi ZHENG Xiao-yong SU Ting-yu HUANG Meng-jie YIN Zhong CHEN Xiang-mei 《中国结合医学杂志:英文版》 SCIE CAS CSCD 2019年第1期37-44,共8页
Objective: To investigate the protective effects and potential mechanisms of Shenhua Tablet(肾华片, SHT) on the toll-like receptors(TLRs)-mediated signaling pathways in a rat model of kidney ischemia-reperfusion injur... Objective: To investigate the protective effects and potential mechanisms of Shenhua Tablet(肾华片, SHT) on the toll-like receptors(TLRs)-mediated signaling pathways in a rat model of kidney ischemia-reperfusion injury(IRI). Methods: Sixty male Wistar rats were randomly divided into 5 groups: sham surgery, model control, astragaloside(150 mg·kg-1·d-1), low-and high-dose SHT(1.5 and 3.0 g·kg-1·d-1, repectively) groups. One week after drug treatment, rats underwent surgery to establish the IRI models. At 24 h and 72 h after the modeling, serum creatinine(Scr) and blood urea nitrogen(BUN) were analyzed; pathological damage were scored after periodic acid-Schiff staining. TLR2, TLR4 and myeloid differentiation factor 88(My D88) protein and m RNA expressions were detected by inmmunohistochemistry, Western blot and qPCR. Tumor necrosis factor α(TNF-α) and interleukin-6(IL-6) protein expressions were detected by enzyme linked immunosorbent assay. Results: Compared with the sham group, the model group exhibited severe change in renal function(Scr: 189.42±21.50, P<0.05), pathological damage(damage score: 4.50±0.55, P<0.05), and the expression levels of TLR2, TLR4, MyD88, TNF-α, IL-6 were significantly higher than other groups. Meanwhile, the levels of TLRs in model group showed upward tendency from 24 to 72 h, unparalleled with pathological and functional changes. The aforementioned parameters were alleviated to a certain extent, and, in addition to TLRs, presented the obvious downward trending from the 24 to 72 h after the intervention in the SHT and astragaloside groups relative to the model(P<0.05); in particular, the most significant mitigation of these changes was observed in the SHT-H group(P<0.05). Conclusions: TLRs may be an important spot to treat and research in acute kidney injury. SHT could effectively mitigate renal injuries and promote recovery of IRI injuries through suppression of degeneration induced by up-regulation of TLR2 and TLR4 expression levels in the My D88-dependent signaling pathway 展开更多
关键词 SHENHUA TABLET Chinese medicine kidney INJURY TOLL-LIKE receptors MYELOID differentiation factor 88 ISCHEMIA-REPERFUSION INJURY
Flavonoids from Scutellaria barbata inhibit activation of tumor-associated macrophages by blocking the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-KB signaling pathway
6
作者 Bao Xiaoxia Li Liuye Xue Xiaoou 《中医杂志:英文版》 SCIE CAS CSCD 2019年第2期160-165,共6页
OBJECTIVE:To determine the efficacy of Scutellaria barbata flavonoids and polysaccharides on Ishikawa endometrial carcinoma cells co-cultured with U937 macrophages.METHODS:The presence of CD163 and CD206 was determine... OBJECTIVE:To determine the efficacy of Scutellaria barbata flavonoids and polysaccharides on Ishikawa endometrial carcinoma cells co-cultured with U937 macrophages.METHODS:The presence of CD163 and CD206 was determined by flow cytometry.Thiazolyl BlueTetrazolium Bromide assays were used to assess the proliferation effect of tumor-associated macrophages(TAMs)on Ishikawa cells.The secretion of interleukin(IL)-10 in the co-culture conditioned media was examined using an enzyme-linked immunosorbent assay.The protein expression levels of Toll-like receptor 4(TLR4)Z myeloid differentiation factor 88(MyD88)and nuclear factor(NF)-kB p65 were detected by Western blot.The mRNA expression levels of TLR4 and MyD88 were analyzed by real-time polymerase chain reaction(PCR).The expression levels of IL-12,IL-1P and tumor necrosis factor-a(TNF-a)were evaluated with real-time PCR.RESULTS:Compared with the U937 control group,the expression levels of CD163 and CD206 in the TAM group were higher(P<0.05).TAMs co-cultured with Ishikawa cells for 24 or 48 h showed higher proliferation rates(P<0.05).The expression levels of IL-12 decreased than compared with those in the U937 untreated group(P<0.05)and those of the Scutellaria barbata flavonoids group(P<0.05).The expression levels of CD206,CD163,IL-10,IL-1|3 and TNF-a,NF-kB p65 and TLR4/MyD88 in the TAMs control group were greater than those in the U937 untreated group(P<0.05)and those of the Scutellaria barbata flavonoids group(P<0.05).CONCLUSION:Scutellaria barbata flavonoids may inhibit TAM activation by blocking the TLR4/MyD88/NF-KB signaling pathway. 展开更多
关键词 ENDOMETRIAL neoplasms SCUTELLARIA baicalensis FLAVONOIDS TOLL-LIKE receptor 4 MYELOID differentiation factor 88 MACROPHAGES
Hepatitis B virus-persistent infection and innate immunity defect:Cell-related or virus-related?
7
作者 Jian Tang Zhen-Yu Wu +2 位作者 Rong-Juan Dai Jing Ma Guo-Zhong Gong 《世界临床病例杂志》 2018年第9期233-241,共9页
The outcomes of hepatitis B virus(HBV)infection are closely related to the age at which infection was acquired.Infection acquired in adult life tends to be selflimited,in contrast to perinatal acquirement,for which ch... The outcomes of hepatitis B virus(HBV)infection are closely related to the age at which infection was acquired.Infection acquired in adult life tends to be selflimited,in contrast to perinatal acquirement,for which chronic persistence of the HBV is a general outcome.Innate immunity plays an indispensable role in early virus infection,facilitating virus clearance.However,it has been reported that HBV is under-recognized and poorly eliminated by the innate immune system in the early stages of infection,possibly explaining the long-lasting persistence of viremia afterwards.Furthermore,due to the existence of covalently closed circular DNA,chronic HBV clearance is very difficult,even when patients are given interferon-αand nucleotide/nucleoside analogs for antiviral therapy.The mechanism by which HBV evades innate immune recognition and establishes persistent infection remains a subject of debate.Besides,some researchers are becoming more interested in how to eradicate chronic HBV infection by restoring or boosting innate immunity.This review aimed to summarize the current knowledge on how intrahepatocyte signaling pathways and innate immune cells act after the onset of HBV infection and how these actions are related to the persistence of HBV.We anticipate the insights presented herein to be helpful for future development of novel immune therapeutic strategies to fight HBV infection. 展开更多
关键词 Hepatitis B virus INNATE immunity Immune EVASION Pattern recognition RECEPTOR TOLL-LIKE RECEPTOR Natural killer CELLS KUPFFER CELLS Dendritic CELLS
在线阅读 免费下载
Drug-containing serum of Xinfeng capsules protect against H9C2 from death by enhancing miRNA-21 and inhibiting toll-like receptor 4/phosphorylated p-38(p-p38)/p-p65 signaling pathway and proinflammatory cytokines expression
8
作者 Cao Yunxiang Guo Yunke +3 位作者 Zong Ruikai Huang Chuanbing Wang Yue Liu Jian 《中医杂志:英文版》 SCIE CAS CSCD 2018年第3期359-365,共7页
OBJECTIVE: To investigate effect of drug-containing serum of Xinfeng capsules on myocardial cell growth.METHODS: Drug-containing serum of Xinfeng capsules rat models were established by intragastricly administrated ... OBJECTIVE: To investigate effect of drug-containing serum of Xinfeng capsules on myocardial cell growth.METHODS: Drug-containing serum of Xinfeng capsules rat models were established by intragastricly administrated Xinfeng capsules. MTT assay wasused to evaluated H9C2 cells viability. H9C2 cells were divided into normal control group, triptolide group, lipopolysaccharide(LPS) group, drug-containing serum group and mi RNA-21 inhibitor group. micro RNA-21(mi RNA-21) inhibitor was structured and transfected into H9C2 cells. Western blot and immunofluorescence assay were applied to examine toll-like receptor 4(TLR4), phosphorylated p-38(p-p38) and p-p65 expression. Quantitative real-time PCR(q RT-PCR) was used to evaluated m RNA levels of mi RNA-21. Enzyme linked immunosorbent(ELISA) was used to measure tumor necrosis factor α(TNF-α), IL-6 and IL-17 levels.RESULTS: Drug-containing serum treatment significantly increased cell viability compared to LPS treated group. q RT-PCR results indicated that mi RNA-21 levels were significantly decreased in drugcontaining serum group compared to LPS group.Early and late apoptosis in drug-containing serum group were significantly decreased compared to LPS group. Western blot and immunofluorescence assay results showed that TLR4, p-p38 and p-p65 levels in drug-containing serum group were significantly decreased compared to LPS group. ELISA findings indicated that drug-containing serum significantly decreased inflammatory cytokine levels of TNF-α, IL-6 and IL-17.CONCLUSION: Drug-containing serum of Xinfeng capsules protect against lipopolysaccharide instructed H9C2 cells from death by enhancing mi RNA-21 and inhibiting TLR4/p-p38/p-p65 signaling pathway and proinflammatory cytokines expression. 展开更多
关键词 Drug-containing SERUM Xinfeng cap-sules MicroRNAs PROINFLAMMATORY cytokines Toll-like receptor 4 Myocardial cell Apoptosis
Influence of Human Papillomavirus E7 Oncoprotein on Maturation and Function of Plasmacytoid Dendritic Cells In Vitro
9
作者 Rui Han Yin-Jing Song +4 位作者 Si-Yuan Sun Qiang Zhou Xian-Zhen Chen Qiao-Li Zheng Hao Cheng 《中国病毒学:英文版》 CAS CSCD 2018年第6期493-501,共9页
The major difficulties of human papillomavirus(HPV) treatment are its persistence and recurrence. The HPV E7 oncoprotein-loaded dendritic cells have been evaluated as cellular vaccine in previous reports. Plasmacytoid... The major difficulties of human papillomavirus(HPV) treatment are its persistence and recurrence. The HPV E7 oncoprotein-loaded dendritic cells have been evaluated as cellular vaccine in previous reports. Plasmacytoid dendritic cells(pDCs) play an essential role of connecting the innate immune response and adaptive immune response in the immune system. But they function in HPV E7 loading is unclear. To investigate whether loading of the HPV type 6b, 11, and 16 E7 proteins affects the activity of pDCs, human peripheral blood-separated pDCs and mouse bone marrow-derived pDCs were pulsed with the HPV E7 proteins. The expression levels of CD40, CD80, CD86, and MHC II were significantly upregulated in pDCs upon HPV 6b/11 E7 protein pulse. The secretion and gene expression of type I IFN and IL-6 were both upregulated by HPV 6b/11 E7 proteins, more significant than HPV 16 E7 protein. The expression of essential factors of TLR signaling pathway and JNK/p38 MAP kinase signaling pathway were all increased in HPV 6b/11 E7 proteins pulsed pDCs. Our results suggest that HPV E7 proteins could promote the differentiation and maturation of pDCs and activate the TLR and MAPK pathway to induce host innate immune response. It might be conducive to explore novel immunotherapy targeting HPV infection with HPV E7 loaded pDC. 展开更多
关键词 Human papillomavirus(HPV) PLASMACYTOID dendritic cells(pDCs) TOLL-LIKE receptors(TLRs) INNATE immunity
Subcellular Localization of Large Yellow Croaker(Larimichthys crocea)TLR21 and Expression Profiling of Its Gene in Immune Response 预览
10
作者 SUN Qingxue FAN Zejun YAO Cuiluan 《中国海洋大学学报:英文版》 SCIE CAS CSCD 2018年第2期335-343,共9页
Toll-like receptor 21(TLR21)is a non-mammalian type TLR,and plays an important role in innate immune response in fish.In this paper,the full-length cDNA sequence of TLR21 gene was identified and characterized from lar... Toll-like receptor 21(TLR21)is a non-mammalian type TLR,and plays an important role in innate immune response in fish.In this paper,the full-length cDNA sequence of TLR21 gene was identified and characterized from large yellow croaker,Larimichthys crocea and was termed as LcTLR21.It consists of 3365 bp,including a 5’-terminal untranslated region(UTR)of 97 bp,a 3’-terminal UTR of 331 bp,and an open reading frame(ORF)of 2937 bp encoding a polypeptide of 978 amino acid residues.The deduced LcTLR21 contains a signal peptide domain at N-terminal,12 leucine-rich repeats(LRRs)at the extracellular region,a transmembrane domain and a cytoplasmic toll-interleukin-1 receptor(TIR)domain at the C-terminal.Subcellular localization analysis revealed that the LcTLR21-GFP was constitutively expressed in cytoplasm.Tissue expression analysis indicated that LcTLR21 gene broadly expressed in most of the examined tissues,with the most predominant abundance in spleen,followed by head-kidney and liver,while the weakest expression was detected in brain.The expression level of LcTLR21 after LPS,poly I:C and Vibrio parahaemolyticus challenges was investigated in spleen,head-kidney and liver.LcTLR21 gene transcripts increased significantly in all examined tissues after the challenges,and the highest expression level was detected in liver at 24 h after poly I:C stimulation(P<0.05),suggesting that LcTLR21 might play a crucial role in fish resistance to viral and bacterial infections. 展开更多
关键词 TOLL-LIKE receptor 21 Larimichthys crocea SUBCELLULAR LOCALIZATION IMMUNE response
在线阅读 下载PDF
白藜芦醇抑制哮喘幼鼠肺组织TLR4与TRIF的表达
11
作者 魏晶 王青筠 +3 位作者 王颖 陆颖 王莹巍 张宝辉 《解剖科学进展》 2018年第5期535-537,541共4页
目的探讨白藜芦醇对哮喘幼鼠肺组织toll样受体4(TLR4)与β干扰素TIR结构域衔接蛋白(TRIF)表达的影响。方法 45只BALB/c幼鼠随机分为对照组、哮喘组和白藜芦醇组。采用卵清蛋白(OVA)刺激,建立幼鼠哮喘模型。HE染色观察各组幼鼠肺... 目的探讨白藜芦醇对哮喘幼鼠肺组织toll样受体4(TLR4)与β干扰素TIR结构域衔接蛋白(TRIF)表达的影响。方法 45只BALB/c幼鼠随机分为对照组、哮喘组和白藜芦醇组。采用卵清蛋白(OVA)刺激,建立幼鼠哮喘模型。HE染色观察各组幼鼠肺组织病理学改变,测定各组幼鼠支气管肺泡灌洗液(BALF)中白细胞总数及嗜酸粒细胞(EOS)数,Western blot方法检测各组幼鼠肺组织TLR4与TRIF的蛋白表达变化,real time PCR方法检测各组幼鼠肺组织TLR4 mRNA与TRIF mRNA的表达水平。结果与对照组相比,哮喘组幼鼠肺组织可见明显的炎性细胞浸润,气道管壁明显增厚,BALF中细胞总数及嗜酸粒细胞计数显著升高,P〈0.01;与哮喘组相比,白藜芦醇组幼鼠肺内炎性细胞浸润明显减轻,BALF中细胞总数及嗜酸粒细胞计数显著降低,P〈0.01。与对照组相比,哮喘组幼鼠肺组织TLR4与TRIF的蛋白与mRNA表达水平显著升高,P〈0.01;与哮喘组相比,白藜芦醇组幼鼠肺组织TLR4与TRIF的蛋白与mRNA表达水平显著降低,P〈0.01。结论白藜芦醇能够抑制哮喘幼鼠肺组织TLR4与TRIF的表达。 展开更多
关键词 哮喘 白藜芦醇 TOLL-LIKE RECEPTOR 4 TRIF 幼鼠
Recombinant expressed vasoactive intestinal peptide analogue ameliorates TNBS-induced colitis in rats
12
作者 Chun-lan Xu Yu Guo +2 位作者 Lei Qiao Li Ma Yi-yi Cheng 《世界胃肠病学杂志:英文版》 SCIE CAS 2018年第6期706-715,共10页
AIM To investigate the modulatory effect of recombinantexpressed vasoactive intestinal peptide(VIP)analogue(rVIPa)on trinitrobenzene sulfonic acid(TNBS)-induced colitis in rats.METHODS Forty-eight rats were randomized... AIM To investigate the modulatory effect of recombinantexpressed vasoactive intestinal peptide(VIP)analogue(rVIPa)on trinitrobenzene sulfonic acid(TNBS)-induced colitis in rats.METHODS Forty-eight rats were randomized into six groups:normal control group(Control),model control group(TNBS),ethanol treatment group(ETOH),and VIP treatment groups with different dosage(rVIPa1nmol,rVIPa2nmol,rVIPa4nmol).Diarrhea and bloody stool were observed.Colonic damage was evaluated histologically.The levels of tumor necrosis factor-α(TNF-α),interleukin-10(IL-10),myeloperoxidase(MPO)and endotoxin in colonic tissue and serum were determined by enzyme-linked immunosorbent assay(ELISA).The expression of occludin,ZO-1,Toll-like receptor 4(TLR4),and nuclear factor-kappa B p65(NF-κB p65),IκBα,and p-IκBαwere detected by Western blot.RESULTS Administration with 2 nmol rVIPa prevented TNBSinduced necrosis,hyperemia,swelling,inflammation,etc.,pathologic changes observed in the inner surface of colon in experimental rats.Moreover,rVIPa significantly decreased colonic TNF-αlevel(P<0.001),MPO activity(P<0.001)and serum endotoxin level(P<0.01),and remarkably increased colonic IL-10 content(P<0.001)in rats with TNBS-induced colitis.Furthermore,compared to the TNBS-induced colitis group,2 nmol rVIPa treatment up-regulated the levels of occludin(P<0.05)and ZO-1(P<0.05),NF-κB p65(P<0.01)and IκBα(P<0.001),and down-regulated the levels of TLR4.CONCLUSION rVIPa ameliorates TNBS-induced colonic injury and inflammation and effectively protected the intestinal mucosal barrier function in rats.The mechanism may be related to TLR4/NF-κB-mediated signaling pathway.rVIPa could be used as a new alternative therapy for intestinal inflammatory disorders. 展开更多
关键词 Vasoactive INTESTINAL peptide INTESTINAL MUCOSAL barrier Tight junction TOLL-LIKE receptors RECOMBINANT expression
在线阅读 免费下载
Activation of natural killer T cells contributes to triptolide-induced liver injury in mice
13
作者 Xin-zhi Wang Ru-feng Xue +3 位作者 Shen-ye Zhang Ya-ting Zheng Lu-yong Zhang Zhen-zhou Jiang 《中国药理学报:英文版》 SCIE CAS CSCD 2018年第12期1847-1854,共8页
Triptolide (TP) is the main active ingredient of Tripterygium wilfordii Hook.f, which has attracted great interest due to its promising efficacy for autoimmune diseases and tumors. However, severe adverse reactions, e... Triptolide (TP) is the main active ingredient of Tripterygium wilfordii Hook.f, which has attracted great interest due to its promising efficacy for autoimmune diseases and tumors. However, severe adverse reactions, especially hepatotoxicity, have restricted its approval in the market. In the present study we explored the role of hepatic natural killer T (NKT) cells in the pathogenesis of TP-induced liver injury in mice. TP (600μg/kg/day, i.g.) was administered to female mice for 1, 3, or 5 days. We found that administration of TP dose-dependently induced hepatotoxicity, evidenced by the body weight reduction, elevated serum ALT and AST levels, as well as significant histopathological changes in the livers. However, the mice were resistant to the development of TP-induced liver injury when their NKT cells were depleted by injection of anti-NK1.1 mAb (200μg, i.p.) on days-2 and-1 before TP administration. We further revealed that TP administration activated NKT cells, dominantly releasing Th1 cytokine IFN-γ, recruiting neutrophils and macrophages, and leading to liver damage. After anti-NK1.1 injection, however, the mice mainly secreted Th2 cytokine IL-4 in the livers and exhibited a significantly lower percentage of hepatic infiltrating neutrophils and macrophages upon TP challenge. The activation of NKT cells was associated with the upregulation of Toll-like receptor (TLR) signaling pathway. Collectively, these results demonstrate a novel role of NKT cells contributing to the mechanisms of TP-induced liver injury. More importantly, the regulation of NKT cells may promote effective measures that control drug-induced liver injury. 展开更多
关键词 TRIPTOLIDE DRUG-INDUCED liver injury natural KILLER T cell Th1/Th2 CYTOKINES IFN-γ IL-4 TOLL-LIKE receptor signaling pathway
Toll-like receptor 4 polymorphisms and bacterial infections in patients with cirrhosis and ascites
14
作者 Edilmar Alvarado-Tapias Carlos Guarner-Argente +11 位作者 Elida Oblitas Elisabet Sánchez Silvia Vidal Eva Román Mar Concepción Maria Poca Cristina Gely Oana Pavel Juan Camilo Nieto Cándido Juárez Carlos Guarner Germán Soriano 《世界肝病学杂志:英文版(电子版)》 2018年第1期124-133,共10页
AIM To assess the relationship between the presence of toll-like receptor 4(TLR4)polymorphisms and bacterial infections in cirrhotic patients with ascites.METHODS We prospectively included consecutive patients with ci... AIM To assess the relationship between the presence of toll-like receptor 4(TLR4)polymorphisms and bacterial infections in cirrhotic patients with ascites.METHODS We prospectively included consecutive patients with cirrhosis and ascites hospitalized during a 6-year period.Patients with human immunodeficiency virus(HIV)infection or any other immunodeficiency,patients with advanced hepatocellular carcinoma(beyond Milan’s criteria)or any other condition determining poor short-term prognosis,and patients with a permanent urinary catheter were excluded.The presence of D299G and/or T399I TLR4 polymorphisms was determined by sequencing and related to the incidence and probability of bacterial infections,other complications of cirrhosis,hepatocellular carcinoma,and mortality during follow-up.A multivariate analysis to identify predictive variables of mortality in the whole series was performed.RESULTS We included 258 patients:28(10.8%)were carriers of D299G and/or T399I TLR4 polymorphisms(polymorphism group)and 230 patients were not(wildtype group).The probability of developing any bacterial infection at one-year follow-up was 78%in the polymorphism group and 69%in the wild-type group(P=0.54).The one-year probability of presenting infections caused by gram-negative bacilli(51%vs 44%,P=0.68),infections caused by gram-positive cocci(49%vs 40%,P=0.53),and spontaneous bacterial peritonitis(29%vs 34%,respectively,P=0.99)did not differ between the two groups.The oneyear probability of transplant-free survival was 55%in the polymorphism group and 66%in the wild-type group(P=0.15).Multivariate analysis confirmed that age,Child-Pugh score,active alcohol intake,previous hepatic encephalopathy,hepatocellular carcinoma and serum creatinine were associated with a higher risk of CONCLUSION Genetic polymorphisms D299G and/or T399I of TLR4 do not seem to play a relevant role in the predisposition of cirrhotic patients with ascites to bacterial infections. 展开更多
关键词 CIRRHOSIS Genetic POLYMORPHISMS TOLL-LIKE receptor 4 BACTERIAL INFECTIONS ASCITES
在线阅读 免费下载
Effect of Shenqi Yangxin decoction on high mobility group box 1and inflammatory signal pathway in a rat model of dilated cardiomyopathy
15
作者 Shen Lijuan Lu Shu +3 位作者 Zhou Yonghua Xing Qingmin Zhou Chungang Li Lan 《中医杂志:英文版》 SCIE CAS CSCD 2018年第6期862-871,共10页
OBJECTIVE:To investigate the effects of Shenqi Yangxin decoction(SQYXD)on heart function in a rat model of dilated cardiomyopathy(DCM)and its potential mechanisms.METHODS:Sprague-Dawley rats were randomly divided into... OBJECTIVE:To investigate the effects of Shenqi Yangxin decoction(SQYXD)on heart function in a rat model of dilated cardiomyopathy(DCM)and its potential mechanisms.METHODS:Sprague-Dawley rats were randomly divided into normal(10 rats)and DCM(150 rats)groups.DCM was induced by an intraperitoneal injection of adriamycin.Then,DCM baseline group was randomly selected sixteen DCM rats.The remaining DCM rats were randomly divided into DCM control,perindopril,metoprolol,and SQYXD groups.Cardiac function and histological analysis plus biochemical measurement of serum levels of brain natriuretic peptide(BNP),and inflammatory factors were measured.The mRNA and protein expression levels of high-mobility group box 1(HMGB1),Toll-like receptor 4(TLR-4),receptor for advanced glycation end products(RAGE),and nuclear factor-κB(NF-κB)were determined.Myocardial metabolism imaging was performed on the normal,SQYXD and DCM control groups to evaluate the effectiveness of treatments.RESULTS:Rats in the DCM control group exhibited dilated left ventricular diameter,impaired cardiac function,disorganized sarcomere,impaired glucose metabolism,increased heart weight index,and increased levels of BNP,which were improved by treatment with SQYXD.In addition,hearts from rats in the DCM baseline group exhibited significantly higher levels of HMGB1,TLR-4,RAGE,NF-κB,tumor necrosis factor-α,interleukin-1,interleukin-6,interleukin-10,compared with the normal group.Interestingly,the mRNA level of HMGB1 in the DCM baseline group was positively correlated with that of TLR-4,RAGE,NF-κB,BNP,and LVEDD,but negatively correlated with LVEF.SQYXD inhibited the upregulation of HMGB1 expression and its downstream inflammatory factors.CONCLUSION:Shenqi Yangxin decoction effectively reduced the dilated left ventricular diameter and improved heart function in dilated cardiomyopathy.The mechanisms underlying the action on DCM involve regulating the gene and protein expression of HMGB1 and its inflammatory signal pathways in the DCM rat model. 展开更多
关键词 Cardiomyopathy dilated Shenqi Yangxin decoction Heart function tests HMGB1 protein TOLL-LIKE RECEPTOR 4 RECEPTOR for advanced glycation end products NF-KAPPA B Treatment outcome
间充质干细胞通过调控TLR信号通路减轻放射所致BV2小胶质细胞炎症反应 被引量:1
16
作者 廖欢 王鸿轩 彭英 《中华神经医学杂志》 CAS CSCD 北大核心 2017年第3期269-273,共5页
目的探讨人间充质干细胞(MSCs)对放射诱导后BV2小胶质细胞中Toll样受体(TLR)信号通路的影响。方法常规培养MSCs及BV2小胶质细胞。实验分为BV2空白对照组、BV2联合MSCs处理组、单纯照射组及BV2照射联合MSCs处理组。BV2细胞放射剂量... 目的探讨人间充质干细胞(MSCs)对放射诱导后BV2小胶质细胞中Toll样受体(TLR)信号通路的影响。方法常规培养MSCs及BV2小胶质细胞。实验分为BV2空白对照组、BV2联合MSCs处理组、单纯照射组及BV2照射联合MSCs处理组。BV2细胞放射剂量为单次照射106y。采用实时荧光定量PCR检测细胞白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、Toll样受体2(TLR2)、Toll样受体4(TLR4)的表达,同时采用酶联免疫吸附测定(ELISA)法检测细胞上清中IL-6和TNF-α的表达。结果实时荧光定量PCR结果显示,单纯照射组细胞IL-6及TNF-α含量较空白对照组明显升高,RV2照射联合MSCs处理组IL-6及TNF—α含量较单纯照射组组细胞明显降低,差异均有统计学意义(P〈0.05)。ELISA实验结果与PCR结果类似。此外,实时荧光定量PCR结果显示,间充质干细胞可下调放射后BV2细胞中TLR2和TLR4的表达。结论MSCs可通过减少TLR信号通路相关因子的释放,抑制放射所致的小胶质细胞炎症反应。 展开更多
关键词 间充质干细胞 小胶质细胞 放射性脑损伤 TOLL样受体信号通路
非髓源性与髓源性细胞Toll样受体4在小鼠肺缺血再灌注损伤中的作用
17
作者 孙明洁 侯念果 +6 位作者 李会 张建华 杨洪光 曹玺 王奕皓 帅训军 艾登斌 《中华麻醉学杂志》 CSCD 北大核心 2017年第7期862-864,共3页
目的 评价非髓源性与髓源性细胞Toll样受体4(TLR4)在小鼠肺缺血再灌注损伤中的作用.方法 健康雄性非髓源性细胞TLR4+/+/髓源性细胞TLR4+/+(WT/WT)小鼠、非髓源性细胞TLR4-/-/髓源性细胞TLR4-/-(KO/KO)纯合体小鼠、非髓源性细... 目的 评价非髓源性与髓源性细胞Toll样受体4(TLR4)在小鼠肺缺血再灌注损伤中的作用.方法 健康雄性非髓源性细胞TLR4+/+/髓源性细胞TLR4+/+(WT/WT)小鼠、非髓源性细胞TLR4-/-/髓源性细胞TLR4-/-(KO/KO)纯合体小鼠、非髓源性细胞TLR4+/+/髓源性细胞TLR4-/-(WT/KO)和非髓源性细胞TLR4-/-/髓源性细胞TLR4+/+(KO/WT)杂合体小鼠各10只,6-8周龄,体重20-25 g.采用阻断左肺门60 min,再灌注240 min的方法制备小鼠肺缺血再灌注损伤模型.于再灌注240 min时采集股动脉血行血气分析,计算氧合指数(PaO2/FiO2),随后处死小鼠取肺组织称湿重(W),烘干后称干重(D),计算W/D比值,光镜下观察肺组织病理学结果,并进行肺损伤评分,采用ELISA法检测髓过氧化物酶(MPO)活性、TNF-α、IL-1β和IL-6的含量.结果 与WT/WT型小鼠比较,WT/KO、KO/WT和KO/KO型小鼠PaO2/FiO2依次升高,肺损伤评分、W/D比值、MPO活性、TNF-α、IL-1β和IL-6含量依次降低(P〈0.05).结论 非髓源性细胞较髓源性细胞TLR4在小鼠肺缺血再灌注损伤中发挥更重要的作用. 展开更多
关键词 TOLL样受体4 再灌注损伤 TOLL-LIKE RECEPTOR 4
TLR4在大鼠坐骨神经损伤后Wallerian溃变过程中的体内作用研究 预览
18
作者 张焕焕 高楠楠 +4 位作者 石玲玉 邵志伟 李雨婷 朱云 姚登兵 《交通医学》 2017年第2期103-107,111共6页
目的:研究TLR4(Toll-likereceptor4)在大鼠坐骨神经损伤后,Wallerian溃变过程中的作用,为周围神经损伤修复与再生的研究提供实验依据。方法:制备大鼠损伤坐骨神经模型;利用修饰过的TLR4基因过表达质粒导入大鼠损伤坐骨神经远端... 目的:研究TLR4(Toll-likereceptor4)在大鼠坐骨神经损伤后,Wallerian溃变过程中的作用,为周围神经损伤修复与再生的研究提供实验依据。方法:制备大鼠损伤坐骨神经模型;利用修饰过的TLR4基因过表达质粒导入大鼠损伤坐骨神经远端组织;通过实时荧光定量PCR和WesternBlot的方法分析损伤7d、ldd后基因和蛋白的表达,以及相关信号通路的变化。结果:在大鼠坐骨神经损伤7d、14d后,实时荧光定量PCR显示,远端TLRd的过表达引起Bax、Bcl-2、NF2、NT3、PKCct等基因的表达变化,WesternBlot显示TLR4过表达后,p-AKT/AKT,p-c-Jull/c-Jun和p-ERK/ERK等蛋白的表达发生显著性差异。结论:TLR4在大鼠坐骨神经损伤后,wallerian溃变过程中可能发挥了重要的调控作用。 展开更多
关键词 Wallerian溃变 TOLL-LIKE RECEPTOR 4 神经再生 大鼠
在线阅读 下载PDF
长链非编码RNA的免疫调控作用及在类风湿关节炎的研究进展
19
作者 沈芹 沈维干 张育 《中华风湿病学杂志》 CSCD 北大核心 2017年第11期783-787,共5页
从1958年Circk提出中心法则,到后来反转录酶的发现,表明非编码序列的存在。这些可以产生稳定转录本的序列称之为非编码RNA(non-coding RNA,ncRNA),细胞中含量最多的ncRNA是tRNA和rRNA,还有snRNA,snoRNA,piRNA,microRNA和长链... 从1958年Circk提出中心法则,到后来反转录酶的发现,表明非编码序列的存在。这些可以产生稳定转录本的序列称之为非编码RNA(non-coding RNA,ncRNA),细胞中含量最多的ncRNA是tRNA和rRNA,还有snRNA,snoRNA,piRNA,microRNA和长链非编码RNA(long non-codingRNA,lncRNA)等。lncRNA是转录本长度超过200nt的非编码RNA,是RNA聚合酶Ⅱ转录的副产物。其生物学功能类似于mRNA,但对于特殊的细胞类型,lncRNA能够实现更精密的调控。根据lncRNA与编码基因位置的关系,分为五大类:基因间、基因内、双向、正义及反义lncRNA。通过分析功能性lncRNA的序列,发现具有如下特征:内含子及起始密码子的缺乏、GC含量的低下以及阅读框的开放。此外,一些lncRNA还具有高级结构,对于发挥特异性功能至关重要。2010年,lncRNA引起研究人员的广泛关注,虽已证实lncRNA几乎在基因生命周期的各个阶段,对基因的表达起调控作用,但具体机制尚需探讨。作为生命科学的重要组成部分,医学领域也日益关注lncRNA在疾病进程中发挥的作用。不少证据显示lncRNA涉及免疫功能的调控,现将与toll样受体(toll-like receptor,TLR)、免疫细胞相关的lncRNA及lncRNA在RA的研究进展作以下综述。 展开更多
关键词 非编码RNA 免疫调控作用 类风湿关节炎 长链 TOLL-LIKE microRNA receptor RNA聚合酶Ⅱ
右美托咪定对肺叶切除术患者围术期血液单核细胞TLR2和TLR4表达的影响
20
作者 刘燕飞 丛丽 +1 位作者 时飞 王彬 《中华麻醉学杂志》 CAS CSCD 北大核心 2015年第9期1044-1046,共3页
目的 评价右美托咪定对肺叶切除术患者围术期血液单核细胞Toll样受体(TLR)2和TLR4表达的影响.方法 择期全麻下行肺叶切除术患者50例,性别不限,年龄40 ~ 64岁,BMI20~ 24 kg/m2,ASA分级Ⅰ或Ⅱ级.采用随机数字表法,将其分为2组(n=25... 目的 评价右美托咪定对肺叶切除术患者围术期血液单核细胞Toll样受体(TLR)2和TLR4表达的影响.方法 择期全麻下行肺叶切除术患者50例,性别不限,年龄40 ~ 64岁,BMI20~ 24 kg/m2,ASA分级Ⅰ或Ⅱ级.采用随机数字表法,将其分为2组(n=25):对照组(C组)和右美托咪定组(D组).D组于麻醉诱导前经10 min静脉输注右美托咪定1.0 μg/kg,继以0.3 μg· kg-1·h-1的速率输注至术毕前30 min;C组给予等容量的生理盐水.于入室、手术开始1.5 h、术毕、术后12h及24 h时采集血样,进行动脉血气分析,计算氧合指数,检测静脉血单核细胞TLR2和TLR4的表达.记录术后48 h内肺部并发症的发生情况.结果 与C组比较,D组静脉血单核细胞TLR2和TLR4表达下调,氧合指数升高,术后肺部并发症发生率降低(P<0.05).结论 右美托咪定减轻肺叶切除术患者急性肺损伤的机制与下调围术期血液单核细胞TLR2和TLR4的表达有关. 展开更多
关键词 右美托咪啶 TOLL样受体2 Toll样受体4 单核细胞 血液 肺切除术 TOLL-LIKE RECEPTOR 2 TOLL-LIKE RECEPTOR 4
上一页 1 2 201 下一页 到第
使用帮助 返回顶部 意见反馈