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虎杖苷对慢性阻塞性肺疾病大鼠气道炎症及TLR4/NF-κB信号通路的影响

Effects of Polydatin on airway inflammation and TLR4/NF-κB signaling pathway in rats with Chronic Obstructive Pulmonary Disease
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摘要 目的:探究虎杖苷对慢性阻塞性肺疾病(COPD)大鼠气道炎症的缓减作用,并初步探究其作用机制。方法:将大鼠随机分为空白对照组、模型组、虎杖苷30、60、120mg/kg组、地塞米松0.09mg/kg组。采用肺功能检测仪检测用力肺活量(FVC)、第0.1秒用力呼气容积(FEV0.1)、呼气峰流速(PEF)、最大呼吸中段气流(MMF)、肺顺应性(Cldyn);吉姆萨染色法检测支气管肺泡灌洗液(BALF)中白细胞总数及中性粒细胞(PMN)、肺泡巨噬细胞(AM)、淋巴细胞(LYM)比例;酶联免疫吸附法检测BALF中TNF-α、IL-8、IL-1β水平;HE染色观察肺组织病理学变化;高碘酸希夫氏染色(PAS)观察支气管病理学变化;免疫印迹法检测肺组织中TLR4、NF-κB、基质金属蛋白酶2(MMP-2)、MMP-9蛋白表达;免疫组化法检测肺组织中TLR4、NF-κB蛋白阳性表达率。结果:与对照组相比,模型组肺组织病理半定量评分显著升高;FVC、FEV0.1、PEF、MMF、Cldyn明显降低,BALF中AM细胞比例明显降低,白细胞总数、PMN、LYM细胞比例明显升高,TNF-α、IL-8、IL-1β水平明显升高,支气管气管壁、平滑肌厚度升高,肺组织中TLR4、NF-κB p65、MMP-2、MMP-9蛋白表达及TLR4、NF-κB p65蛋白阳性表达率明显升高。与模型组相比,虎杖苷各组、地塞米松组肺组织病理半定量评分显著降低。FVC、FEV0.1、PEF、MMF、Cldyn升高,BALF中AM细胞比例显著升高,白细胞总数、PMN、LYM细胞比例显著降低,TNF-α、IL-8、IL-1β水平显著降低,支气管气管壁、平滑肌厚度降低,肺组织中TLR4、NF-κB p65、MMP-2、MMP-9蛋白表达及TLR4、NF-κB p65蛋白阳性表达率显著降低。结论:虎杖苷可改善肺组织、支气管组织形态,降低大鼠气道炎症反应,其机制可能与抑制TLR4/NF-κB信号通路有关。 Objective:To explore the effect of polydatin on the airway inflammation in rats with chronic obstructive pulmonary disease(COPD)and its mechanism.Methods:Rats were randomly divided into the control group,COPD model group(model group),polydatin groups at doses of 30、60 and 120 mg/kg,0.09 mg/kg dexamethasone group.Forced vital capacity(FVC),the forced expiratory volume in 0.1 second(FEV0.1),peak expiratory flow(PEF),maximum mid-expiratory flow(MMF)and complianc Lung dynamics(Cldyn)were measured with a pulmonary function detector.The total number of leukocytes and the proportion of polymorphonuclearleukocyte(PMN),alveolar macrophage(AM)and lymphocyte(LYM)cells in bronchoalveolar lavage fluid(BALF)were detected by Jimsa staining method.Levels of TNF-α,IL-8 and IL-1βin BALF were detected by ELISA.Pathological changes of lung tissues were observed by HE staining.Bronchial pathological changes were observed by Periodate Schiff’s staining(PAS).Protein expressions of TLR4,NF-κB,matrix metalloproteinase-2(MMP-2)and MMP-9 in lung tissues were detected by Western blotting.Positive expression rates of TLR4 and NF-κB protein in lung tissues were detected by immunohistochemistry.Results:Compared with the control group,the pathological semi-quantitative scores of lung tissues in the model group were significantly increased.FVC,FEV0.1,PEF,MMF,Cldyn in the model group were decreased,AM cell proportion in BALF was decreased,the total number of white blood cell,PMN and LYM cell proportion was increased,levels of TNF-α,IL-8,IL-1βwere increased.The thickness of bronchial tracheal wall and smooth muscle were increased,protein expressions of TLR4,NF-κB p65,MMP-2,MMP-9 and protein positive expression rates of TLR4,NF-κB p65 in lung tissues were significantly increased.Compared with the model group,the pathological semi-quantitative scores of lung tissues in polydatin group and dexamethasone group were significantly decreased.FVC,FEV0.1,PEF,MMF and Cldyn in polydatin group and DXM group were increased,AM cell proportion in BAL
作者 周勇 余洋 程文涛 肖璠 Zhou Yong;Yu Yang;Cheng Wentao;Xiao Fan(Tuberculosis District,Jinyintan Hospital in Wuhan City,Wuhan,Hubei 430023)
出处 《中药药理与临床》 CAS CSCD 北大核心 2019年第2期35-40,共6页 Pharmacology and Clinics of Chinese Materia Medica
基金 湖北省卫生和计划生育委员会科研立项项目(编号WJ2017F043).
关键词 慢性阻塞性肺疾病 虎杖苷 气道炎症 TOLL样受体4 核因子ΚB Chronic obstructive pulmonary disease Polydatin Airway inflammation Toll-like receptor 4 Nuclear factorκB
作者简介 通讯作者:肖璠,邮箱463147476@qq.com;第一作者:周勇,硕士,主治医师,研究方向:主要从事呼吸系统疾病基础与临床研究工作,邮箱:zhouyong7619@163.com。
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