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miR-199a-3p对脂肪变性的肝细胞TG含量及Sp1表达的影响 预览
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作者 侯天禄 陈天阳 成扬 《胃肠病学和肝病学杂志》 CAS 2019年第6期660-663,共4页
目的 研究miR-199a-3p对脂肪变性的肝细胞TG含量及Sp1表达的影响,明确其具体机制。方法 建立肝细胞脂肪变性体外模型。分别用miR-199a-3p模拟物、抑制剂、阴性对照(NC)及pcDNA3.1-Sp1质粒转染细胞48 h,收集细胞样本,以PCR检测 mRNA 表... 目的 研究miR-199a-3p对脂肪变性的肝细胞TG含量及Sp1表达的影响,明确其具体机制。方法 建立肝细胞脂肪变性体外模型。分别用miR-199a-3p模拟物、抑制剂、阴性对照(NC)及pcDNA3.1-Sp1质粒转染细胞48 h,收集细胞样本,以PCR检测 mRNA 表达水平,Western blotting分析检测蛋白表达,试剂盒检测TG含量。结果 与NC组相比,转染miR-199a-3p模拟物后,细胞内miR-199a-3p表达显著升高(P<0.05);细胞内FASN、SREBP1表达显著降低(P<0.01),细胞内Sp1 mRNA表达显著降低(P<0.05);细胞内TG含量显著降低(P<0.05);细胞内Sp1蛋白表达显著降低(P<0.01)。转染miR-199a-3p抑制剂后,细胞内miR-199a-3p表达显著降低(P<0.01);细胞内FASN和SREBP1表达显著升高(P<0.05);细胞内TG含量显著升高(P<0.05)。转染miR-199a-3p模拟物和pcDNA3.1-Sp1后,细胞内FASN及SREBP1的表达升高,细胞内TG含量显著升高,Hepa 1-6细胞内Sp1蛋白表达显著升高(P<0.01)。结论 miR-199a-3p可以抑制Sp1的表达,降低脂肪变性肝细胞内TG含量,改善肝细胞脂肪变性,但其确切机制有待进一步深入研究。 展开更多
关键词 miR-199a-3p 脂肪变性 TG SP1
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Intestinal permeability after Mediterranean diet and low-fat diet in non-alcoholic fatty liver disease 预览
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作者 Marco Biolato Fiorella Manca +7 位作者 Giuseppe Marrone Consuelo Cefalo Simona Racco Giacinto A Miggiano Venanzio Valenza Antonio Gasbarrini Luca Miele Antonio Grieco 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第4期509-520,共12页
BACKGROUND In non-alcoholic fatty liver disease(NAFLD),a high-fat or high-fructose diet increases intestinal permeability and promotes derangement of the gut-liver axis.We hypothesize that,diet could be able to modula... BACKGROUND In non-alcoholic fatty liver disease(NAFLD),a high-fat or high-fructose diet increases intestinal permeability and promotes derangement of the gut-liver axis.We hypothesize that,diet could be able to modulate intestinal permeability in patients with NAFLD.AIM To detect diet-induced modification of intestinal permeability in patients with NAFLD undergoing a Mediterranean diet or a low-fat diet.METHODS The current study was a dietary intervention for non-diabetic,patients with biopsy-verified NAFLD and increased transaminases.A crossover design was employed:participants underwent 16 weeks of Mediterranean diet,16 wk of free wash-out,and 16 weeks of low-fat diet.Both diets were hypocaloric and no consumption of supplements was allowed.All patients were followed bimonthly by a dietitian.Evaluations of clinical and metabolic parameters were completed at baseline and at the end of each dietary period.Intestinal permeability was assessed by chromium-51 ethylene diamine tetraacetate excretion testing(51Cr-EDTA).RESULTS Twenty Caucasian patients,90%male,median age 43 years,body mass index(BMI)30.9,with biopsy-verified NAFLD were enrolled.At the end of 16 weeks of a Mediterranean diet,a significant reduction in mean body weight(-5.3±4.1 kg,P=0.003),mean waist circumference(-7.9±4.9 cm,P=0.001),and mean transaminase levels[alanine aminotransferase(ALT)-28.3±11.9 IU/L,P=0.0001;aspartate aminotransferase(AST)-6.4±56.3 IU/L,P=0.01]were observed.These benefits were maintained after 16 wk of wash-out and also after 16 wk of low-fat diet,without further improvements.Fourteen of the 20 patients had intestinal permeability alteration at baseline(mean percentage retention of 51Cr-EDTA=5.4%),but no significant changes in intestinal permeability were observed at the end of the 16 wk of the Mediterranean diet or 16 wk of the low-fat diet.CONCLUSION Mediterranean diet is an effective strategy for treating overweight,visceral obesity and serum transaminase in patients with NAFLD.If the Mediterranean diet can improve intest 展开更多
关键词 LIVER STEATOSIS Gut-liver axis NUTRITION PERSONALIZED medicine VISCERAL obesity
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美他多辛通过诱导细胞自噬抑制肝细胞脂肪变性的作用机制研究
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作者 王海舫 黄静 +2 位作者 张岁 贾蓓 杨大伟 《中国临床药理学杂志》 CAS CSCD 北大核心 2019年第16期1752-1755,共4页
目的研究自噬在美他多辛(MTD)抑制肝细胞脂肪变性中的作用。方法用0.5mmol·L-1油酸(OA)处理人肝癌细胞株(HepG2)24h建立肝细胞脂肪变性模型。将细胞分为4组:空白组、模型组、对照组和实验组。在模型细胞的基础上,对照组加30μmol&#... 目的研究自噬在美他多辛(MTD)抑制肝细胞脂肪变性中的作用。方法用0.5mmol·L-1油酸(OA)处理人肝癌细胞株(HepG2)24h建立肝细胞脂肪变性模型。将细胞分为4组:空白组、模型组、对照组和实验组。在模型细胞的基础上,对照组加30μmol·L-1MTD继续处理24h;实验组加10mmol·L-13-甲基腺嘌呤(3-MA)处理1h后,加入30μmol·L-1MTD处理23h;空白组给予等体积的溶剂处理。以细胞脂质比色法检测细胞脂质含量,以蛋白免疫印迹法检测自噬标志蛋白MAP1LC3B2和细胞溶质内激素敏感脂酶(HSL)的表达水平。结果空白组、模型组、对照组和实验组的脂质含量(OD值)分别为0.16±0.04,0.32±0.08,0.21±0.02和0.26±0.07,模型组与空白组比较,或者对照组和实验组与模型组比较,差异均有统计学意义(均P<0.05);上述这4组的MAP1LC3B2/β-actin分别为0.51±0.07,0.62±0.04,1.21±0.12和0.71±0.09;上述这4组的p-T-HSL/β-actin分别为0.16±0.05,2.13±0.24,1.34±0.16和1.79±0.13,对照组与模型组比较,MAP1LC3B2表达显著增加;实验组能明显抑制MTD诱导的MAP1LC3B2的表达;模型组中p-HSL水平明显高于空白组;对照组p-HSL水平明显低于模型组,上述指标的差异均有统计学意义(均P<0.05)。结论美他多辛能通过诱导自噬而改善OA引起的肝细胞脂肪变性。 展开更多
关键词 HEPG2细胞 肝脂肪变性 美他多辛 自噬
Diabetic cardiomyopathy:Pathophysiology,theories and evidence to date 预览
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作者 Lavanya Athithan Gaurav S Gulsin +1 位作者 Gerald P McCann Eylem Levelt 《世界糖尿病杂志:英文版(电子版)》 2019年第10期490-510,共21页
The prevalence of type 2 diabetes(T2D)has increased worldwide and doubled over the last two decades.It features among the top 10 causes of mortality and morbidity in the world.Cardiovascular disease is the leading cau... The prevalence of type 2 diabetes(T2D)has increased worldwide and doubled over the last two decades.It features among the top 10 causes of mortality and morbidity in the world.Cardiovascular disease is the leading cause of complications in diabetes and within this,heart failure has been shown to be the leading cause of emergency admissions in the United Kingdom.There are many hypotheses and well-evidenced mechanisms by which diabetic cardiomyopathy as an entity develops.This review aims to give an overview of these mechanisms,with particular emphasis on metabolic inflexibility.T2D is associated with inefficient substrate utilisation,an inability to increase glucose metabolism and dependence on fatty acid oxidation within the diabetic heart resulting in mitochondrial uncoupling,glucotoxicity,lipotoxicity and initially subclinical cardiac dysfunction and finally in overt heart failure.The review also gives a concise update on developments within clinical imaging,specifically cardiac magnetic resonance studies to characterise and phenotype early cardiac dysfunction in T2D.A better understanding of the pathophysiology involved provides a platform for targeted therapy in diabetes to prevent the development of early heart failure with preserved ejection fraction. 展开更多
关键词 DIABETIC CARDIOMYOPATHY Cardiac metabolism MYOCARDIAL STEATOSIS MYOCARDIAL strain
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Tibolone Reverses NAFLD in Ovariectomised Rats by Reducing Adiposity and Insulin Resistance 预览
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作者 Lilian Brites Campos-Shimada Eduardo Hideo Gilglioni +5 位作者 Danielle Aparecida Munhos Hermoso Ana Julia dos Reis Buzzo Rosangela Fernandes Garcia Elismari Rizato Martins-Maciel Emy Luiza Ishii-Iwamoto Clairce Luzia Salgueiro-Pagadigorria 《药剂与药理学:英文版》 2019年第4期148-164,共17页
This study aimed to investigate the effects of tibolone,a synthetic steroid,on several metabolic dysfunctions induced by oestrogen deficiency,in rats.Ovariectomised(OVX)rats were used as animal model of postmenopausal... This study aimed to investigate the effects of tibolone,a synthetic steroid,on several metabolic dysfunctions induced by oestrogen deficiency,in rats.Ovariectomised(OVX)rats were used as animal model of postmenopausal metabolic syndrome.The OVX rats were treated with daily doses of tibolone(0.16 mg/kg)and the results were compared with control(sham-operated)and OVX untreated rats.Tibolone reduced the adiposity and the visceral adipocyte size in OVX rats.The insulin sensitivity was also improved,and a decrease in the activity of the adipose tissue hormone-sensitive lipase enzyme was recorded.The lower lipolysis by visceral adipocytes,associated with the recovery of peroxisomalβ-oxidation by tibolone may have contributed to the reversion of NAFLD in treated OVX rats.The reduction of liver lipid contents resulted in a general improvement in the liver redox state.In addition,tibolone reduced the mitochondrial ROS generation and restored the activity of glucose-6-phosphate dehydrogenase.Tibolone also exerted antioxidant effects on inguinal adipose tissue.Tibolone exerted several beneficial effects on cellular and metabolic dysfunctions induced by ovariectomy in rats.One important mode of action of tibolone was the reduction of the visceral adipocyte size,corroborating the relationship between this one and the development and progression of several comorbidities associated with metabolic syndrome. 展开更多
关键词 TIBOLONE OVARIECTOMY hepatic STEATOSIS obesity OXIDATIVESTRESS
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Chronic hepatitis B and metabolic risk factors:A call for rigorous longitudinal studies 预览
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作者 Wai-Kay Seto 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第3期282-286,共5页
Long-term nucleos(t)ide analogue therapy in chronic hepatitis B virus(HBV)infection is effective in suppressing viral replication and reducing liver-related complications.However,HBV-related liver events can still occ... Long-term nucleos(t)ide analogue therapy in chronic hepatitis B virus(HBV)infection is effective in suppressing viral replication and reducing liver-related complications.However,HBV-related liver events can still occur in different patient sub-groups.There is emerging evidence that,similar to chronic hepatitis C virus infection,metabolic risk factors may play a role in the disease process of chronic HBV.While the mechanistic nature of metabolic-HBV interactions remains uncertain,studies in different HBV-infected populations have demonstrated that hepatic steatosis,increased body-mass index,diabetes,or a combination of different metabolic risk factors are associated with an increased risk of hepatocellular carcinoma and cirrhosis.The impact of metabolic risk factors is especially prominent in patients with quiescent virological activity,including on-treatment patients with effective viral suppression.As the proportion of on-treatment chronic HBV patients increases worldwide,longitudinal studies determining the relative risks of different metabolic parameters with respect to clinical outcomes are needed.Future studies should also determine if metabolic-directed interventions can improve disease outcomes in chronic HBV. 展开更多
关键词 HEPATITIS B virus Diabetes OBESITY STEATOSIS Non-alcoholic FATTY liver disease BODY-MASS index
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果糖诱导肝脂肪变性细胞模型建立及评价 预览
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作者 贺雯茜 杨金玉 +3 位作者 徐艳娇 兰露露 张程亮 刘东 《肝脏》 2019年第6期638-642,共5页
目的 建立果糖诱导L02肝细胞脂肪变性模型的方法,并对该细胞模型脂质合成进行评价。方法 体外培养L02肝细胞,以不同浓度的果糖处理24h诱导细胞脂肪变性。Cck-8法检测果糖对细胞的活性影响,检测培养液中ALT、AST含量变化以确定果糖对肝... 目的 建立果糖诱导L02肝细胞脂肪变性模型的方法,并对该细胞模型脂质合成进行评价。方法 体外培养L02肝细胞,以不同浓度的果糖处理24h诱导细胞脂肪变性。Cck-8法检测果糖对细胞的活性影响,检测培养液中ALT、AST含量变化以确定果糖对肝细胞的损伤。油红O染色观察胞内脂滴沉积情况,并测定胞内三酰甘油(TG)含量,确定最佳模型浓度;同时利用蛋白印迹检测碳水化合物反应元件结合蛋白(ChREBP)、固醇调节元件结合蛋白-1c(SREBP-1c)、乙酰辅酶A羧化酶1(ACC1)和硬脂酰辅酶A去饱和酶1(SCD1)蛋白表达,并与游离脂肪酸(FFA)干预相比较。结果 L02肝细胞在0~32mmol/L果糖干预下活性无显著改变,细胞无显著损伤。果糖浓度为4mmol/L时,L02肝细胞内即有大量脂滴形成。且细胞内TG含量显著增加,为正常对照的1.5倍。4mmol/L果糖能显著上调ChREBP、SREBP-1和ACC1蛋白表达。相对于FFA,果糖对SCD1和ACC1蛋白表达上调更显著。结论 采用4mmol/L果糖可成功诱导L02肝细胞脂肪变性,该模型适用于高果糖饮食诱发的非酒精性脂肪性肝病脂质合成研究。 展开更多
关键词 果糖 非酒精性脂肪性病 细胞模型 脂肪变性 脂质从头合成
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雌激素对人肝癌HepG2细胞脂肪变性的作用及AQP7表达的影响 预览
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作者 傅晓华 朱晶 舒静 《浙江医学》 CAS 2019年第18期1928-1931,1937,I0005共6页
目的探讨雌激素对人肝癌Hep G2细胞脂肪变性的作用及水通道蛋白7(AQP7)表达的影响。方法将培养后的人肝癌HepG2细胞分为HepG2细胞组、脂肪变模型组、雌激素低剂量组、雌激素高剂量组;其中脂肪变模型组及雌激素低、高剂量组使用2.0m M油... 目的探讨雌激素对人肝癌Hep G2细胞脂肪变性的作用及水通道蛋白7(AQP7)表达的影响。方法将培养后的人肝癌HepG2细胞分为HepG2细胞组、脂肪变模型组、雌激素低剂量组、雌激素高剂量组;其中脂肪变模型组及雌激素低、高剂量组使用2.0m M油酸溶液200μl处理,而雌激素低、高剂量组分别加入500μl浓度为40.0、80.0μg/ml的雌激素,HepG2细胞组不作任何处理;4组细胞均继续培养72h。采用噻唑蓝(MTT)法测定细胞存活率,油红O溶液染色法测定脂滴面积比,贝克曼AU-480全自动生化仪测定TG水平,RT-PCR、Western blot法分别测定HepG2细胞AQP7 mRNA及蛋白相对表达量。结果与HepG2细胞组比较,脂肪变模型组细胞存活率降低(P<0.05),脂滴面积比、TG水平均升高(均P<0.05);与脂肪变模型组比较,雌激素低、高剂量组细胞存活率均升高(均P<0.05),脂滴面积比、TG水平均降低(均P<0.05);与雌激素低剂量组比较,雌激素高剂量组细胞存活率升高(P<0.05),脂滴面积比、TG水平均降低(均P<0.05)。与HepG2细胞组比较,脂肪变模型组AQP7 mRNA及蛋白相对表达量均降低(均P<0.05);与脂肪变模型组比较,雌激素低、高剂量组AQP7 mRNA及蛋白相对表达量均升高(均P<0.05);与雌激素低剂量组比较,雌激素高剂量组AQP7 mRNA及蛋白相对表达量均升高(均P<0.05)。HepG2细胞AQP7 mRNA及蛋白相对表达量与脂滴面积比、TG水平均呈负相关(均P<0.05)。结论雌激素能抑制油酸诱导的HepG2细胞脂肪变性,其机制可能与雌激素能上调AQP7表达有关。 展开更多
关键词 雌激素 HEPG2细胞 脂肪变性 水通道蛋白7
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氧化苦参碱抗慢性肝损伤的药理作用及其机制研究进展
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作者 张明发 沈雅琴 《药物评价研究》 CAS 2019年第7期1466-1473,共8页
氧化苦参碱具有抗高脂饮食性、CCl4性、CCl4/酒精性、二甲基亚硝胺性、半乳糖胺性、免疫性慢性肝损伤作用。氧化苦参碱是通过抗氧化、抗炎作用,减轻肝脏的氧化应激和炎症反应以及抑制成纤维细胞和肝星状细胞的活化以及细胞外基质生成,... 氧化苦参碱具有抗高脂饮食性、CCl4性、CCl4/酒精性、二甲基亚硝胺性、半乳糖胺性、免疫性慢性肝损伤作用。氧化苦参碱是通过抗氧化、抗炎作用,减轻肝脏的氧化应激和炎症反应以及抑制成纤维细胞和肝星状细胞的活化以及细胞外基质生成,产生抗肝纤维化作用。氧化苦参碱还可通过促进胰岛素信号转导,改善胰岛素抵抗,抑制肝细胞吸收长链脂肪酸和脂肪酸合成并加速游离脂肪酸的β-氧化,产生抗脂肪肝作用。 展开更多
关键词 氧化苦参碱 慢性肝损伤 肝脂肪变 肝纤维化
miR-222 targets ACOX1,promotes triglyceride accumulation in hepatocytes 预览
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作者 Jing-Jie Wang Yi-Tong Zhang +1 位作者 Yu Jen Tseng Jun Zhang 《国际肝胆胰疾病杂志:英文版》 SCIE CAS CSCD 2019年第4期360-365,共6页
Background:Non-alcoholic fatty liver disease(NAFLD)is one of the most prevalent chronic liver diseases.However,the exact pathogenesis of NAFLD remains to be elucidated.Despite the association with tumors and cardiovas... Background:Non-alcoholic fatty liver disease(NAFLD)is one of the most prevalent chronic liver diseases.However,the exact pathogenesis of NAFLD remains to be elucidated.Despite the association with tumors and cardiovascular diseases,the role of miR-222 in NAFLD remains unclear.The present study was to investigate the role of miR-222 in NAFLD.Methods:Wild-type C57BL/6 mice were fed a high-fat diet for 12 weeks to induce NAFLD.Normal human liver cell line(L02)was cultured with free fatty acid(FFA)-containing medium to stimulate cell steatosis.The mRNA levels of miR-222 and acyl Coenzyme A xidase 1(ACOX1)were detected by quantitative-PCR(Q-PCR).The prediction of ACOX1 as the target gene for miR-222 was conducted via TargetScan.The overexpression or inhibition of miR-222 was mediated by miR-222 mimics or antagomir,and intracellular triglyceride levels were measured using a triglyceride kit.Luciferase reporter assays verified ACOX1 as the target gene for miR-222.Results:miR-222 was significantly elevated in both the in vivo and in vitro NAFLD models.Overexpression of miR-222 significantly increased triglyceride content in the L02 cells,while inhibition of miR-222 expression restricted the accumulation of triglyceride.Overexpression of miR-222 significantly inhibited ACOX1 expression.Transient transfection assays verified that ACOX1 3-UTR luciferase reporter activity could be inhibited by miR-222 overexpression.Conclusions:The present study suggested that miR-222 promotes the accumulation of triglycerides by inhibiting ACOX1. 展开更多
关键词 ACOX1 Hepatocyte steatosis MIR-222 NAFLD β-hydroxybutyrate
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Hepatocellular carcinoma and metabolic syndrome: The times are changing and so should we 预览
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作者 Georgios Tsoulfas 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第29期3842-3848,共7页
Although hepatocellular carcinoma (HCC) is as prevalent as ever as a cancerrelated mortality, and some would even argue that it is increasing, the pattern of its etiologies has been changing. Specifically, the dominat... Although hepatocellular carcinoma (HCC) is as prevalent as ever as a cancerrelated mortality, and some would even argue that it is increasing, the pattern of its etiologies has been changing. Specifically, the domination of viral hepatitis C virus is being overcome, partly because of the emergence of the antiviral treatments, and partly because of the significant increase, especially in developed countries, of the combination of obesity, diabetes, metabolic syndrome, nonalcoholic fatty liver disease and non-alcoholic steatohepatitis. This editorial will explore the interconnection of this group of diseases and how they are linked to HCC. More importantly, it will argue that this shift in HCC etiology essentially means that we have to change how we approach the treatment of HCC, by changing our focus (and resources) to earlier stages of the disease development in order to prevent the appearance and progression of HCC. 展开更多
关键词 Hepatocellular carcinoma Diabetes Obesity STEATOSIS Non-alcoholic fatty liver disease BODY-MASS index Non-alcoholic STEATOHEPATITIS
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Noninvasive evaluation of nonalcoholic fatty liver disease: Current evidence and practice 预览
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作者 Jiang-Hua Zhou Jing-Jing Cai +1 位作者 Zhi-Gang She Hong-Liang Li 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第11期1307-1326,共20页
With the increasing number of individuals with diabetes and obesity,nonalcoholic fatty liver disease(NAFLD) is becoming increasingly prevalent,affecting one-quarter of adults worldwide. The spectrum of NAFLD ranges fr... With the increasing number of individuals with diabetes and obesity,nonalcoholic fatty liver disease(NAFLD) is becoming increasingly prevalent,affecting one-quarter of adults worldwide. The spectrum of NAFLD ranges from simple steatosis or nonalcoholic fatty liver(NAFL) to nonalcoholic steatohepatitis(NASH). NAFLD, especially NASH, may progress to fibrosis, leading to cirrhosis and hepatocellular carcinoma. NAFLD can impose a severe economic burden,and patients with NAFLD-related terminal or deteriorative liver diseases have become one of the main groups receiving liver transplantation. The increasing prevalence of NAFLD and the severe outcomes of NASH make it necessary to use effective methods to identify NAFLD. Although recognized as the gold standard, biopsy is limited by its sampling bias, poor acceptability, and severe complications, such as mortality, bleeding, and pain. Therefore, noninvasive methods are urgently needed to avoid biopsy for diagnosing NAFLD. This review discusses the current noninvasive methods for assessing NAFLD,including steatosis, NASH, and NAFLD-related fibrosis, and explores the advantages and disadvantages of measurement tools. In addition, we analyze potential noninvasive biomarkers for tracking disease processes and monitoring treatment effects, and explore effective algorithms consisting of imaging and nonimaging biomarkers for diagnosing advanced fibrosis and reducing unnecessary biopsies in clinical practice. 展开更多
关键词 NONALCOHOLIC fatty liver disease NONALCOHOLIC STEATOHEPATITIS STEATOSIS FIBROSIS NONINVASIVE EVALUATION
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Hemodynamic changes in hepatic sinusoids of hepatic steatosis mice 预览
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作者 Jing Fan Chong-Jiu Chen +3 位作者 Yu-Chen Wang Wei Quan Jian-Wei Wang Wei-Guang Zhang 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第11期1355-1365,共11页
BACKGROUND Fatty liver(FL) is now a worldwide disease. For decades, researchers have been kept trying to elucidate the mechanism of FL at the molecular level, but rarely involve the study of morphology and medical phy... BACKGROUND Fatty liver(FL) is now a worldwide disease. For decades, researchers have been kept trying to elucidate the mechanism of FL at the molecular level, but rarely involve the study of morphology and medical physics. Traditionally, it was believed that hemodynamic changes occur only when fibrosis occurs, but it has been proved that these changes already show in steatosis stage, which may help to reveal the pathogenesis and its progress. Because the pseudolobules are not formed during the steatosis stage, this phenomenon may be caused by the compression of the liver microcirculation and changes in the hemodynamics.AIM To understand the pathogenesis of hepatic steatosis and to study the hemodynamic changes associated with hepatic steatosis.METHODS Eight-week-old male C57 BL/6 mice were divided into three groups randomly(control group, 2-wk group, and 4-wk group), with 16 mice per group. A hepatic steatosis model was established by subcutaneous injection of carbon tetrachloride in mice. After establishing the model, liver tissue from mice was stained with hematoxylin and eosin(HE), and oil red O stains. Blood was collected from the angular vein, and hemorheological parameters were estimated. A two-photon fluorescence microscope was used to examine the flow properties of red blood cells in the hepatic sinusoids.RESULTS Oil red O staining indicated lipid accumulation in the liver after CCl4 treatment.HE staining indicated narrowing of the hepatic sinusoidal vessels. No significant difference was observed between the 2-wk and 4-wk groups of mice onmorphological examination. Hemorheological tests included whole blood viscosity(mPas, γ = 10 s-1/γ = 100 s-1)(8.83 ± 2.22/4.69 ± 1.16, 7.73 ± 2.46/4.22 ±1.32, and 8.06 ± 2.88/4.22 ± 1.50), red blood cell volume(%)(51.00 ± 4.00, 42.00 ±5.00, and 40.00 ± 3.00), the content of plasma fibrinase(g/L)(3.80 ± 0.50, 2.90 ±0.80, and 2.30 ± 0.70), erythrocyte deformation index(%)(44.49 ± 5.81, 48.00 ±15.29, and 44.36 ± 15.01), erythrocyte electrophoresis rate(mm/ 展开更多
关键词 HEPATIC STEATOSIS HEMODYNAMICS HEPATIC SINUSOIDS TWO-PHOTON fluorescence microscopy Carbon TETRACHLORIDE
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Bariatric surgery in patients with non-alcoholic fatty liver disease-from pathophysiology to clinical effects 预览
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作者 Tea L Laursen Christoffer A Hagemann +4 位作者 Chunshan Wei Konstantin Kazankov Karen L Thomsen Filip K Knop Henning Grφb?k 《世界肝病学杂志:英文版(电子版)》 2019年第2期138-149,共12页
Non-alcoholic fatty liver disease(NAFLD)is increasingly recognized as a significant liver disease,and it covers the disease spectrum from simple steatosis with a risk of development of non-alcoholic steatohepatitis(NA... Non-alcoholic fatty liver disease(NAFLD)is increasingly recognized as a significant liver disease,and it covers the disease spectrum from simple steatosis with a risk of development of non-alcoholic steatohepatitis(NASH)to fibrosis,subsequent cirrhosis,end-stage liver failure,and liver cancer with a potential need for liver transplantation.NAFLD and NASH are closely related to obesity,metabolic syndrome,and type 2 diabetes(T2D).The role of gut hormones,especially glucagon-like peptide 1(GLP-1),is important in NAFLD.Bariatric surgery has the potential for inducing great weight loss and may improve the symptoms of metabolic syndrome and T2D.Recent data demonstrated significant effects of bariatric surgery on GLP-1 and other gut hormones and important lipid metabolic and inflammatory abnormalities in the pathophysiology of NAFLD.Therefore,bariatric surgery may reverse the pathological liver changes in NAFLD and NASH patients.In the present review,we describe NAFLD and NASH pathophysiology and the primary effects of bariatric surgery on metabolic pathways.We performed a systematic review of the beneficial and harmful effects and focused on changes in liver disease severity in NAFLD and NASH patients.The specific focus was liver histopathology as assessed by the invasive liver biopsy.Additionally,we reviewed several non-invasive methods used for the assessment of liver disease severity following bariatric surgery. 展开更多
关键词 Non-alcoholic fatty liver disease Non-alcoholic STEATOHEPATITIS BARIATRIC surgery Insulin resistance Gut hormones Glucagon-like peptide 1 STEATOSIS Inflammation Fibrosis
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Allyl isothiocyanate ameliorates lipid accumulation and inflammation in nonalcoholic fatty liver disease via the Sirt1/AMPK and NF-κB signaling pathways 预览
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作者 Chun-Xiao Li Jian-Guo Gao +9 位作者 Xing-Yong Wan Yi Chen Cheng-Fu Xu Ze-Min Feng Hang Zeng Yi-Ming Lin Han Ma Ping Xu Chao-Hui Yu You-Ming Li 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第34期5120-5133,共14页
BACKGROUND Allyl isothiocyanate(AITC),a classic anti-inflammatory and antitumorigenic agent,was recently identified as a potential treatment for obesity and insulin resistance.However,little is known about its direct ... BACKGROUND Allyl isothiocyanate(AITC),a classic anti-inflammatory and antitumorigenic agent,was recently identified as a potential treatment for obesity and insulin resistance.However,little is known about its direct impact on the liver.AIM To investigate the effect and underlying mechanism of AITC in nonalcoholic fatty liver disease(commonly referred to as NAFLD).METHODS To establish a mouse and cellular model of NAFLD,C57BL/6 mice were fed a high fat diet(HFD)for 8 wk,and AML-12 cells were treated with 200μM palmitate acid for 24 h.For AITC treatment,mice were administered AITC(100 mg/kg/d)orally and AML-12 cells were treated with AITC(20μmol/L).RESULTS AITC significantly ameliorated HFD-induced weight gain,hepatic lipid accumulation and inflammation in vivo.Furthermore,serum alanine aminotransferase and aspartate aminotransferase levels were markedly reduced in AITC-treated mice.Mechanistically,AITC significantly downregulated the protein levels of sterol regulatory elementbinding protein 1(SREBP1)and its lipogenesis target genes and upregulated the levels of proteins involved in fatty acidβ-oxidation,as well as the upstream mediators Sirtuin 1(Sirt1)and AMPactivated protein kinaseα(AMPKα),in the livers of HFD-fed mice.AITC also attenuated the nuclear factor kappa B(NF-κB)signaling pathway.Consistently,AITC relieved palmitate acid-induced lipid accumulation and inflammation in AML-12 cells in vitro through the Sirt1/AMPK and NF-κB signaling pathways.Importantly,further studies showed that the curative effect of AITC on lipid accumulation was abolished by siRNA-mediated knockdown of either Sirt1 or AMPKαin AML-12 cells.CONCLUSION AITC significantly ameliorates hepatic steatosis and inflammation by activating the Sirt1/AMPK pathway and inhibiting the NF-κB pathway.Therefore,AITC is a potential therapeutic agent for NAFLD. 展开更多
关键词 ALLYL ISOTHIOCYANATE NONALCOHOLIC fatty LIVER disease Hepatic STEATOSIS LIVER INFLAMMATION
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D-ribose increases triglyceride via upregulation of DGAT in the liver
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作者 Yao Chen Lexiang Yu +4 位作者 Yan Wei Yang Long Yong Xu Tao He Rongqiao He 《中国科学:生命科学英文版》 SCIE CAS CSCD 2019年第6期858-861,共4页
Dear Editor, Fatty liver disease or hepatic steatosis, recognized as the hepatic component of metabolic syndrome, can progress to cirrhosis and hepatocellular carcinoma (Youngwanichsetha, 2018).
关键词 DEAR Editor hepatic STEATOSIS progress to cirrhosis
Biomarkers and subtypes of deranged lipid metabolism in nonalcoholic fatty liver disease 预览
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作者 José M Mato Cristina Alonso +1 位作者 Mazen Noureddin Shelly C Lu 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第24期3009-3020,共12页
Nonalcoholic fatty liver disease(NAFLD)is a heterogeneous and complex disease that is imprecisely diagnosed by liver biopsy.NAFLD covers a spectrum that ranges from simple steatosis,nonalcoholic steatohepatitis(NASH)w... Nonalcoholic fatty liver disease(NAFLD)is a heterogeneous and complex disease that is imprecisely diagnosed by liver biopsy.NAFLD covers a spectrum that ranges from simple steatosis,nonalcoholic steatohepatitis(NASH)with varying degrees of fibrosis,to cirrhosis,which is a major risk factor for hepatocellular carcinoma.Lifestyle and eating habit changes during the last century have made NAFLD the most common liver disease linked to obesity,type 2 diabetes mellitus and dyslipidemia,with a global prevalence of 25%.NAFLD arises when the uptake of fatty acids(FA)and triglycerides(TG)from circulation and de novo lipogenesis saturate the rate of FAβ-oxidation and verylow density lipoprotein(VLDL)-TG export.Deranged lipid metabolism is also associated with NAFLD progression from steatosis to NASH,and therefore,alterations in liver and serum lipidomic signatures are good indicators of the disease’s development and progression.This review focuses on the importance of the classification of NAFLD patients into different subtypes,corresponding to the main alteration(s)in the major pathways that regulate FA homeostasis leading,in each case,to the initiation and progression of NASH.This concept also supports the targeted intervention as a key approach to maximize therapeutic efficacy and opens the door to the development of precise NASH treatments. 展开更多
关键词 S-ADENOSYLMETHIONINE Methionine adenosyltransferase Lipid METABOLISM Multiomics LIPIDOMICS Nonalcoholic steatohepatitis One-carbon METABOLISM Very LOW-DENSITY LIPOPROTEINS STEATOSIS Precision medicine
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Role of sodium-glucose co-transporter-2 inhibitors in the management of nonalcoholic fatty liver disease 预览
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作者 Anastasia Kontana Konstantinos Tziomalos 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第28期3664-3668,共5页
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. NAFLD is considerably more frequent in patients with type 2 diabetes mellitus (T2DM) than in the general populat... Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. NAFLD is considerably more frequent in patients with type 2 diabetes mellitus (T2DM) than in the general population and is also more severe histologically in this group. Sodium-glucose co-transporter-2 (SGLT2) inhibitors, the newest class of antidiabetic agents, appear to represent a promising option for the management of NAFLD in patients with T2DM. In a number of studies, treatment with SGLT2 inhibitors resulted in a reduction in hepatic steatosis and in transaminase levels. However, existing studies are small, their follow-up period was short and none evaluated the effects of SGLT2 inhibitors on liver histology. Accordingly, larger studies are needed to verify these preliminary results and define the role of SGLT2 inhibitors in the treatment of NAFLD in patients with T2DM. 展开更多
关键词 NONALCOHOLIC fatty liver disease Type 2 diabetes mellitus Sodium-glucose co-transporter-2 INHIBITORS STEATOSIS Fibrosis TRANSAMINASES
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木香烃内酯抑制乙醇诱导的肝细胞损伤与脂肪变性 预览
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作者 班笃敬 魏炜 +2 位作者 申超 缪雪华 刘文生 《天然产物研究与开发》 CAS CSCD 北大核心 2019年第4期608-614,共7页
探究木香烃内酯体外对乙醇诱导肝细胞损伤及脂肪变性的影响。建立乙醇导致人LO2肝细胞损伤模型,检测木香烃内酯对细胞活力、ALT和AST释放、脂质生成、脂质调控因子表达及AMPK活性的影响。发现乙醇在高于100mM浓度时显著抑制肝细胞活力,... 探究木香烃内酯体外对乙醇诱导肝细胞损伤及脂肪变性的影响。建立乙醇导致人LO2肝细胞损伤模型,检测木香烃内酯对细胞活力、ALT和AST释放、脂质生成、脂质调控因子表达及AMPK活性的影响。发现乙醇在高于100mM浓度时显著抑制肝细胞活力,据此将100mM浓度的乙醇作为体外刺激肝细胞的实验浓度。木香烃内酯能够逆转乙醇对肝细胞活力的抑制作用,并降低乙醇导致的肝细胞ALT、AST的释放。木香烃内酯能够降低乙醇诱导的肝细胞脂质成分集聚,降低细胞内TG、TC水平。此外,乙醇导致肝细胞中重要的脂质调控转录因子SREBP-1c的表达显著上调,使PPARα的表达显著下调;而木香烃内酯能够减少SREBP-1c的表达并增加PPARα的表达。进一步发现,木香烃内酯显著促进肝细胞中AMPK的磷酸化,且AMPK抑制剂BML-275能够显著削弱木香烃内脂对SREBP-1c和PPARα的调控作用。综上,木香烃内酯体外显著改善乙醇诱导的肝细胞损伤与脂肪变性,该作用与激活AMPK进而调控SREBP-1c与PPARα的表达有关。本研究为将木香烃内酯作为抗酒精性脂肪肝候选药物研究提供实验依据。 展开更多
关键词 木香烃内酯 酒精性脂肪肝 肝细胞 脂肪变性 AMPK
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Ursodeoxycholic acid ameliorates hepatic lipid metabolism in LO2 cells by regulating the AKT/mTOR/SREBP-1 signaling pathway 预览
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作者 Jie Hu Wei Hong +3 位作者 Kan-Nan Yao Xiao-Hong Zhu Zhi-Yun Chen Lei Ye 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第12期1492-1501,共10页
BACKGROUND Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease, can progress into nonalcoholic steatohepatitis (NASH), cirrhosis, and even hepatocellular carcinoma. Bile acids such as ursod... BACKGROUND Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease, can progress into nonalcoholic steatohepatitis (NASH), cirrhosis, and even hepatocellular carcinoma. Bile acids such as ursodeoxycholic acid (UDCA) play an essential role in the pathogenesis of NAFLD by regulating the level of sterol regulatory element-binding protein (SREBP) 1c, but the underlying regulatory mechanism remains elusive. Increased evidence indicates that the AKT/mTOR/SREBP-1 signaling pathway is a key pathway to regulate hepatic cellular lipid metabolism. UDCA may regulate the AKT/mTOR/SREBP-1 signaling pathway to ameliorate hepatic lipid metabolism. AIM To investigate the functional mechanism of UDCA in an oleic acid (OA)-induced cellular model of NAFLD. METHODS The cellular model of NAFLD was established using OA and treated with UDCA. First, the best concentration of UDCA was selected. For the best time-dependent assay, cells were stimulated with OA only or co-treated with OA and 2 mmol/L UDCA for 24 h, 48 h, and 72 h. Oil red O staining was used to observe the accumulation of intracellular lipids, while the intracellular contents of triglyceride, alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), and aspartate aminotransferase (AST) were detected by enzymatic methods. Meanwhile, the expression levels of AKT/mTOR/SREBP-1 signaling pathway-related proteins were detected by real-time PCR and Western blot.RESULTS In the NAFLD cell model established with LO2 cells induced using OA, lipid accumulation was obvious. UDCA significantly inhibited lipid accumulation at different concentrations (especially 2 mmol/L) and decreased cell growth ability at different time points. The biochemical parameters like ALT, AST, and GGT were significant improved by UDCA. UDCA treatment vividly repressed the activation of AKT, mTOR, and CRTC2 and the expression of nSREBP-1 in LO2 cells induced with OA. CONCLUSION Our findings demonstrate the effect of UDCA in improving NAFLD. UDCA attenuates OA-induced hepatic s 展开更多
关键词 Ursodeoxycholic acid HEPATIC LIPID metabolism AKT/mTOR/SREBP-1 HEPATIC STEATOSIS
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