AACO方调控TGF-β1/Smad3信号通路保护慢性心力衰竭小鼠心肌纤维化的作用机制研究  

Study on Mechanism of AACO Prescription for Regulating TGF-β1/Smad3 Signaling Pathway to Protect Myocardial Fibrosis in Mice with Chronic Heart Failure

作　　者：王新婷 鲁成[3] 宋磊[4] 钟逸航 刘永明[1,2] WANG Xinting;LU Cheng;SONG Lei;ZHONG Yihang;LIU Yongming(Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Branch of National Clinical Research Center for Chinese Medicine Cardiology,Shanghai 201203,China;The Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200137,China;Traditional Chinese Medicine of Luan,Lu'an 237000,China)

机构地区：[1]上海中医药大学附属曙光医院,上海201203 [2]国家中医心血管临床医学研究中心分中心,上海201203 [3]上海中医药大学附属第七人民医院,上海200137 [4]六安市中医院,安徽六安237000

出　　处：《中国中医药信息杂志》2023年第1期103-108,共6页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金(81973611);上海市青年科技英才扬帆计划(20YF1436800);上海市临床重点专科(中医心病科)项目(shslczdzk05301)。

摘　　要：目的基于TGF-β1/Smad3信号通路探讨AACO方防治慢性心力衰竭(CHF)心肌纤维化的可能作用机制。方法将40只C57BL/6J小鼠随机分为假手术组、模型组、AACO方组和卡维地洛组,每组10只。采用主动脉弓缩窄术建立CHF小鼠模型,分别予相应药物灌胃,假手术组和模型组予等量双蒸水灌胃,连续8周。超声心动图检测小鼠心脏功能;HE染色观察心脏病理变化;Masson染色和苦味酸天狼猩红染色检测心脏组织胶原容积分数(CVF)和纤维化程度;免疫荧光染色检测心脏组织α-平滑肌肌动蛋白(α-SMA)和Ⅰ型胶原(ColⅠ)表达;RT-qPCR检测心尖组织ColⅠ、ColⅢmRNA表达;Western blot检测心尖组织α-SMA、转化生长因子β1(TGF-β1)、Smad3、p-Smad3蛋白表达。结果与假手术组比较,模型组小鼠左室射血分数(LVEF)、左室短轴缩短率(FS)显著减少,左室舒张末期内径(LVIDd)显著增加(P<0.01),心肌细胞排列紊乱,心肌间质疏松,心脏组织CVF、纤维化面积比显著增加(P<0.01),心尖组织ColⅠ、ColⅢmRNA及TGF-β1、p-Smad3、α-SMA、ColⅠ蛋白表达均显著升高(P<0.05,P<0.01);与模型组比较,AACO方组小鼠LVEF、FS显著增加,LVIDd显著减少(P<0.01),心肌细胞排列较为规则,心脏组织CVF、纤维化面积比显著减少(P<0.05,P<0.01),心尖组织ColⅠ、ColⅢmRNA及TGF-β1、p-Smad3、α-SMA、ColⅠ蛋白表达均显著降低(P<0.05,P<0.01)。结论AACO方可显著抑制CHF模型小鼠心肌纤维化,其机制可能与抑制TGF-β1/Smad3信号通路有关。Objective To explore the mechanism of the AACO Prescription in the prevention and treatment of myocardial fibrosis in chronic heart failure(CHF)based on TGF-β1/Smad3 signaling pathway.Methods Totally 40C57BL/6J mice were randomly divided into sham-operation group,model group,AACO Prescription group,and carvedilol group,with 10 mice in each group.The CHF mouse model was established by transverse aortic coarctation.The mice were given corresponding drugs by gavege for 8 weeks,and the sham-operation group and the model group were given the same amount of double-distilled water for gavage.The cardiac function was detected by echocardiography,the pathological changes of cardiac were observed by HE staining,CVF and the degree of cardiac fibrosis was detected by Masson staining and Sirius red picrate staining,the expressions ofα-SMA and ColⅠin cardiac tissue were detected by immunofluorescence staining,the expressions ofα-SMA,TGF-β1,Smad3 and p-Smad3 protein in apical tissue were detected by Western blot,the expressions of ColⅠand ColⅢmRNA in apical tissue were detected by RT-q PCR.Results Compared with the sham-operation group,the LVEF and FS of mice in the model group significantly reduced,LVIDd significantly increased(P<0.01),cardiomyocyte arrangement disordered and myocardial interstitial loosed,while CVF of cardiac and ratio of fibrotic area significantly increased(P<0.01),the expressions of ColⅠ,ColⅢmRNA and TGF-β1,p-Smad3,α-SMA,ColⅠprotein in apical tissue significantly increased(P<0.05).Compared with the model group,the LVEF and FS of mice in the AACO Prescription group significantly increased,LVIDd significantly reduced(P<0.01),cardiomyocytes were arranged regularly,while CVF of cardiac and ratio of fibrotic area significantly reduced(P<0.05,P<0.01),the expressions of ColⅠ,ColⅢmRNA and TGF-β1,p-Smad3,α-SMA,ColⅠprotein in apical tissue decreased significantly(P<0.05,P<0.01).Conclusion AACO Prescription can significantly inhibit myocardial fibrosis of CHF mice,and the possible mechanism

关 键 词：AACO方 慢性心力衰竭 心肌纤维化 TGF-β1/Smad3信号通路 

分 类 号：R285.5[医药卫生—中药学]