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基于TGF-β1/Smad2/3信号通路研究芪参六味方对自发性高血压大鼠心肌纤维化的影响

Mechanism of Qishen Liuwei formula on myocardial fibrosis in SHR through TGF-β1/Smad2/3 pathway
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摘要 目的:采用芪参六味方干预自发性高血压大鼠(SHR)心肌纤维化(MF)模型,观察其对大鼠MF的影响并探讨其作用机制。方法:SHR大鼠15只,分为模型组、中药组和氯沙坦钾组,每组5只。另魏-凯二氏大鼠(WKY)5只作为对照组。干预12周后检测各组大鼠超声心动图,处死后取左室心肌组织进行相关检测。采用Masson染色及苦味酸-天狼猩红染色,观察心肌组织胶原含量与分布;采用Western blot法测定各组大鼠心肌组织中Ⅰ型胶原(CollagenⅠ)、Ⅲ型胶原(CollagenⅢ)、基质金属蛋白酶(MMP)-9、基质金属蛋白酶抑制剂(TIMP)-1、转化生长因子(TGF)-β1、Smad2、Smad3蛋白的表达;采用RT-PCR法检测TGF-β1、Smad2、Smad3 mRNA的表达。结果:干预12周后,与模型组比较,中药组镜下胶原纤维明显减少,排列较均匀,E/E’、心肌组织胶原纤维面积百分比、CollagenⅠ/CollagenⅢ明显降低(P<0.05),CollagenⅠ、CollagenⅢ、MMP-9、TGF-β1、Smad2、Smad3蛋白表达量均降低(P<0.05),TGF-β1、Smad2 mRNA表达量下降(P<0.05)。结论:芪参六味方可通过调控TGF-β1/Smad2/3信号通路,减轻细胞外基质的沉积,改善SHR大鼠心肌纤维化。 Objective:To investigate the effect and mechanism of Qishen Liuwei formula on myocardial fibrosis in spontaneously hypertensive rats.Methods:SHR were divided into model group,Qishen Liuwei formula group,and losartan potassium group,with 5 rats in each group.5 WYK were selected as the control group.After 12 weeks of intervention,the echocardiography was detected,and then the rats were killed,and myocardial tissue were taken for relevant testing.Masson staining and picric acid-sirius scarlet staining were used to observe the content and distribution of myocardial collagen.The Western blot method was used to determine the expression of CollagenⅠ,CollagenⅢ,MMP-9,TIMP-1,TGF-β1,Smad2 and Smad3 proteins in the myocardial tissues of rats.RT-PCR was used to detect the expression of TGF-β1,Smad2 and Smad3 mRNA.Results:After 12 weeks of intervention,compared with the model group,the microscopic collagen fibers in the Qishen Liuwei formula group were reduced and the arrangement was more uniform,E/E’,the percentage of collagen fiber area of myocardial tissue and CollagenⅠ/CollagenⅢwere reduced(P<0.05),and the expression of CollagenⅠ,CollagenⅢ,MMP-9,TGF-β1,Smad2 and Smad3 proteins were decreased(P<0.05),TGF-β1,Smad2 mRNA expression levels were reduced(P<0.05).Conclusion:Qishen Liuwei formula can reduce the deposition of extracellular matrix and improve the myocardial fibrosis in SHR rats by regulating the TGF-β1/Smad2/3 pathway.
作者 惠嫣然 董菲 贾文浩 肖华丽 余林波 黄丽君 毛天诗 林谦 周鹍 HUI Yanran;DONG Fei;JIA Wenhao;XIAO Huali;YU Linbo;HUANG Lijun;MAO Tianshi;LIN Qian;ZHOU Kun(Beijing University of Chinese Medicine,Beijing 100029,China)
出处 《陕西中医》 CAS 2023年第10期1337-1343,共7页 Shaanxi Journal of Traditional Chinese Medicine
基金 国家自然科学基金资助面上项目(81874385)。
关键词 自发性高血压 芪参六味方 心肌纤维化 TGF-β1/Smad2/3信号通路 大鼠 Spontaneous hypertensive Qishen Liuwei formula Myocardial fibrosis TGF-β1/Smad2/3 pathway Rats
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