基于β1-AR/TGF-β1/Smad2通路探讨稳心颗粒对异丙肾上腺素诱导的大鼠心肌纤维化的影响  

The effects of Wenxin Granules on isoproterenol-induced myocardial fibrosis in rats throughβ1-AR/TGF-β1/Smad2 pathway

作　　者：于露 邓芳隽 梁嘉钰 樊博雅 钱舒乐 李晓凤[2] YU Lu;DENG Fangjun;LIANG Jiayu;FAN Boya;QIAN Shule;LI Xiaofeng(Tianjin University of Traditional Chinese Medicine,Tianjin 300383,China)

机构地区：[1]天津中医药大学,300383 [2]天津中医药大学第二附属医院心血管科

出　　处：《环球中医药》2024年第8期1507-1514,共8页Global Traditional Chinese Medicine

基　　金：国家自然科学基金(82004329);天津市中医药管理局天津市名中医传承工作建设项目“杜武勋天津市名中医传承工作室”;国家中医药管理局全国名老中医药专家传承工作室建设项目“杜武勋全国名老中医药专家传承工作室”;天津市教委科研计划(2019SK025)。

摘　　要：目的探讨稳心颗粒通过β1-AR/TGF-β1/Smad2通路对异丙肾上腺素(isoproterenol,ISO)诱导大鼠心肌纤维化的影响。方法雄性SD大鼠60只,随机分为对照组、ISO组与稳心颗粒低、中、高剂量组以及胺碘酮组,每组10只,连续给药14天。第15天起,ISO组、各药物组大鼠以ISO 5 mg/(kg•d)皮下多点注射构建大鼠心肌纤维化模型。检测大鼠心脏质量指数的变化;采用苏木素—伊红(hematoxylin-eosin,HE)染色观察心肌形态学变化,Masson染色观察心肌胶原分布和含量变化;检测心肌组织羟脯氨酸(hydroxyproline,HYP)和谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-PX)的含量;蛋白免疫印迹法(Western blot,WB)检测大鼠心肌组织交感神经系统-β1肾上腺素能受体(β1 adrenoceptor,β1-AR)、转化生长因子β1(transforming growth factor-β,TGF-β1)、p-Smad2蛋白表达变化。结果ISO组大鼠心脏质量指数明显升,细胞结构紊乱,胶原沉积和心肌纤维化明显,心肌HYP含量显著增多,GSH含量减少,β1-AR、TGF-β1与p-Smad2表达水平显著升高(P<0.01);与ISO组相比,各治疗组心脏质量指数降低,细胞结构损伤与胶原沉积减轻,心肌纤维化改善,HYP含量降低,GSH含量增多,β1-AR、TGF-β1与p-Smad2表达水平明显降低(P<0.05,P<0.01)。稳心颗粒高剂量组效果较稳心颗粒低剂量组更为明显(P<0.05),与胺碘酮组相比无明显差异(P>0.05)。结论稳心颗粒能够改善ISO引起的心肌纤维化,减轻心肌细胞损伤与胶原纤维堆积,其机制可能与β1-AR/TGF-β1/Smad2通路有关。Objective To observe the effects of Wenxin Granules on isoproterenol(ISO)-induced myocardial fibrosis in rats throughβ1-AR/TGF-β1/Smad2 pathway.Methods 60 male Sprague Dawley(SD)rats were randomly divided into six groups:control group,ISO group,Wenxin Granules low-dose,middle-dose,and high-dose groups,and amiodarone group,with 10 rats in each group.The drugs were continuously given for 14 days.Starting from day 15,rats in ISO group,and treatment groups were given the hypodermic multi-point injection of ISO for 14 consecutive days to establish the myocardial fibrosis model in rats.The changes of heart weight index in rats were detected.The cardiac morphological changes were observed by hematoxylin-eosin staining(HE),and the changes in cardiac collagen distribution and content were observed by Masson staining.The levels of HYP,GSH-PX,sympathetic nervous system-β1 adrenergic receptor(β1-AR),transforming growth factorβ1(TGF-β1)and p-Smad2 in rat myocardial were determined.Results Compared with rats of control group,the heart weight index in rats of ISO group were obviously elevated,the cellular structure was disordered,and collagen deposition and myocardial fibrosis were significant.Myocardial HYP levels were markedly elevated,and the GSH levels were obviously reduced.The myocardialβ1-AR,TGF-β1 and p-Smad2 levels of ISO group rats were significantly increased(P<0.05,P<0.01).While compared to rats of ISO group,the heart weight index of rats in each treatment groups were decreased,the cardiac structural disorder and collagen deposition were alleviated,and myocardial fibrosis was significantly improved,the HYP levels showed a significant decrease and the GSH levels showed a slight increase,andβ1-AR,TGF-β1and p-Smad2 levels were decreased(P<0.05,P<0.01).The therapeutic effect of high-dose Wenxin Granules group was more remarkable than that in low-dose Wenxin Granules group(P<0.05),with no obvious difference compared with amiodarone group.Conclusion Wenxin Granules can improve ISO-induced myocardial fibrosis,all

关 键 词：稳心颗粒 异丙肾上腺素 心肌纤维化 交感神经系统-β1肾上腺素能受体 转化生长因子β1 SMAD2 

分 类 号：R285.5[医药卫生—中药学]