环黄芪醇对异丙肾上腺素诱导小鼠心肌纤维化的影响  

Effects of cycloastragenol on cardiac fibrosis induced by isoproterenol in mice

作　　者：董雪 范宏伟 胡丙雪 张茵[1] 张朝[1] DONG Xue;FAN Hong-wei;HU Bing-xue;ZHANG Yin;ZHANG Zhao(Jiangsu Key Laboratory for Molecular and Medical Biotechnology,College of Life Sciences,Nanjing Normal University,Nanjing 210023,China)

机构地区：[1]南京师范大学生命科学学院,江苏省分子与医学技术重点实验室,江苏南京210023

出　　处：《中国病理生理杂志》2020年第3期385-393,共9页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.31171302);江苏省教育厅自然科学研究计划重大项目(No.16KJA18000);江苏省优势学科资助项目(No.1164320H106)。

摘　　要：目的:探讨环黄芪醇(cycloastragenol,CAG)对小鼠心肌纤维化的影响及其机制。方法:用异丙肾上腺素(isoproterenol,ISO)建立小鼠心肌纤维化模型,用低、高浓度CAG分别处理小鼠。超声心动法检测小鼠心功能;Masson三色染色法观察心脏纤维化情况;RT-qPCR、Western blot和免疫组织化学法检测与纤维化相关的信号分子表达。此外,分离培养乳大鼠心脏成纤维细胞,检测上述信号分子的表达。结果:CAG显著缓解了ISO刺激所致的心脏功能紊乱和心肌纤维化;抑制了氧化应激相关因子NADPH氧化酶4和诱导型一氧化氮合酶的转录;抑制了核因子κB信号通路中关键蛋白的磷酸化以及转化生长因子β(transforming growth factor-β,TGF-β)的表达;并且在原代成纤维细胞中验证了CAG可以缓解ISO刺激引起的上述因子表达。结论:CAG通过抑制氧化应激、炎症反应和TGF-β的表达缓解心肌纤维化。AIM: To investigate the effects of cycloastragenol(CAG) on cardiac fibrosis in mice and the mechanism involved. METHODS: The mouse model of cardiac fibrosis induced by isoproterenol(ISO) was established and treated with high-and low-dose CAG. Cardiac function was measured by echocardiography, and heart sections were stained by Masson’s trichrome for fibrosis assessment. The expression of fibrosis-related factors was assayed using RT-qPCR, Western blot and immunohistochemistry. In addition, cardiac fibroblasts isolated from neonatal factors rat ventricles were cultured and administrated with ISO followed by CAG treatment, and then the expression profile of the factors above was assayed using RT-qPCR. RESULTS: Treatment with CAG significantly alleviated ISO-induced cardiac dysfunction and fibrosis, inhibited the mRNA expression of oxidative stress-related factors NADPH oxidase 4 and inducible nitric oxide synthase, and blocked the phosphorylation of proteins associated with nuclear factor-κB signaling pathway as well as the expression of transforming growth factor-β(TGF-β). In addition, it was demonstrated that CAG also inhibited the mRNA expression of the factors above in primary cardiac fibroblasts administrated with ISO.CONCLUSION: CAG markedly rescues ISO-induced cardiac dysfunction and fibrosis via inhibition of oxidative stress, inflammation and TGF-β levels.

关 键 词：环黄芪醇 心肌纤维化 氧化应激 核因子ΚB 转化生长因子Β 

分 类 号：R542.2[医药卫生—心血管疾病] R363.2[医药卫生—内科学]