文献类型：期刊文献

中文题名：基于TGF-β1/Smads信号通路探讨芪参益心颗粒对心力衰竭大鼠心肌纤维化的影响

英文题名：Effect of Qishen Yixin Granule on Myocardial Fibrosis in Rats with Heart Failure based on TGF-β1/Smads Signaling Pathway

作者：徐鑫[1];王记[1];寇宗莉[1];杨开燕[1];李淑玲[1];王洁[1];魏惠平[1]

第一作者：徐鑫

机构：[1]甘肃中医药大学附属医院,甘肃兰州730010

第一机构：甘肃中医药大学第二附属医院

年份：2025

卷号：37

期号：9

起止页码：1769

中文期刊名：中医药临床杂志

外文期刊名：Clinical Journal of Traditional Chinese Medicine

基金：中医药传承与创新“百千万”人才工程(岐黄工程)青年岐黄学者基金资助项目;甘肃中医药大学附属医院创新(gzfy-2-22-10)。

语种：中文

中文关键词：芪参益心颗粒;心力衰竭;心肌纤维化;TGF-β1/Smads信号通路

外文关键词：Qishen Yixin granule;Heart failure;Myocardial fibrosis;TGF-β1/Smads signaling pathway

摘要：目的:探究芪参益心颗粒对阿霉素(DOX)诱导的心力衰竭(HF)心肌纤维化及TGF-β1/Smads信号通路的影响,以探讨机制。方法:将40只Wistar雄性大鼠随机分为空白组、模型组、芪参益心颗粒组、盐酸贝那普利组。除空白组外,其余各组大鼠腹腔注射DOX(2.5 mg·kg^(-1)、累积剂量15mg·kg^(-1))1次/周造模。造模后24h末,芪参益心颗粒组予以芪参益心颗粒(5.6g·kg^(-1))生理盐水溶解液灌胃、盐酸贝那普利组予以盐酸贝那普利(0.9mg·kg^(-1))生理盐水溶解液灌胃,模型组以等容积生理盐水灌胃,空白组不干预,共4周。末次给药结束后,采用心脏彩超评价大鼠心功能,HE染色观察大鼠心肌组织病理变化,Masson染色观察心肌纤维化,蛋白免疫印迹法(Wesern blot)法检测心肌组织TGF-β1、Smad2、Smad3蛋白表达,Elisa法检测大鼠血清C-反应蛋白(CRP)、白细胞介素4、6、18(IL-4、IL-6、IL-18)等炎症因子表达,透射电镜观察大鼠心肌超微结构的变化。结果:与空白组比较,模型组左心室射血分数(LVEF)、短轴缩短率(FS)降低(P<0.05);心肌组织TGF-β1、Smad2、Smad3蛋白表达升高(P<0.05);血清CRP、IL-4、IL-6及IL-18表达升高(P<0.05);心肌细胞排列紊乱、肌纤维断裂,并有炎性细胞浸润等病理改变;纤维化面积及程度显著;大鼠心肌细胞Z线、肌丝排列紊乱、断裂及溶解,线粒体肿胀及发生线粒体自噬,内质网、高尔基复合体结构破坏。与模型组比较,贝那普利组、芪参益心颗粒组LVEF、FS升高(P<0.05);心肌组织TGF-β1、Smad2、Smad3蛋白表达显著降低(P<0.05);血清CRP、IL-4、IL-6及IL-18的表达减少(P<0.05);大鼠心肌细胞排列较整齐、肌纤维断裂较少、少量炎性细胞浸润等病理改变;纤维化面积及程度减轻;心肌细胞Z线、肌丝排列较整齐,线粒体肿胀及自噬减轻,内质网、高尔基复合体结构破坏减轻。结论:芪参益心颗粒可能通过调控TGF-β1/Smads信号通路对HF心肌纤维化具有一定的延缓作用。
Objective:To investigate the effects of Qishen Yixin Granule on myocardial fibrosis and the TGF-β1/Smads signaling pathway in doxorubicin(DOX)-induced heart failure(HF)and to explore the underlying mechanism.Methods:Forty male Wistar rats were randomly divided into a blank group,a model group,a Qishen Yixin Granule group,and a benazepril hydrochloride group.Except for the blank group,rats in all other groups received intraperito-neal injections of DOX(2.5 mg/kg,cumulative dose 15 mg/kg)once weekly to establish HF models.At the end of 24 hours after model establishment,the Qishen Yixin Granule group received Qishen Yixin Granule(5.6 g//kg)dissolved in saline by gavage,while the benazepril hydrochloride group received benazepril hydrochloride(0.9 mg/kg)dissolved in saline by gavage.The model group received an equal volume of saline by gavage.The blank group received no inter-vention for a total of 4 weeks.After the last administration,cardiac function of rats was evaluated by cardiac ultrasound,myocardial tissue pathological changes were observed by HE staining,myocardial fibrosis was observed by Masson staining,the expression of TGF-β1,Smad2,and Smad3 proteins in myocardial tissue was detected by Western blot,the expression of inflammatory factors such as CRP,IL-4,IL-6,and IL-18 in rat serum was detected by ELISA,and the changes in myocardial ultrastructure were observed by transmission electron microscopy.Results:Compared with the blank group,the LVEF and FS of the model group were decreased(P<0.05);the expressions of TGF-β1,Smad2,and Smad3 proteins in myocardial tissue were increased(P<0.05);the expressions of serum CRP,IL-4,IL-6,and IL-18 were increased(P<0.05);the myocardial cells were disordered,myofibers were ruptured,and there was inflammatory cell infiltration;the area and degree of fibrosis were significant;the Z lines and myofilaments of myocardial cells were disordered,ruptured,and dissolved;the mitochondria were swollen and mitophagy occurred;and the structures of the endoplasmic reticulum and Golgi complex were destroyed.Compared with the model group,the benazepril and Qishen Yixin granule groups showed increased LVEF and FS(P<0.05).Myocardial tissue TGF-β1,Smad2,and Smad3 pro-tein expressions were significantly decreased(P<0.05).Serum CRP,IL-4,IL-6,and IL-18 expressions were also re-duced(P<0.05).Pathological changes included more regular myocardial cell arrangement,fewer myofiber ruptures,and a small amount of inflammatory cell infiltration.The area and degree of fibrosis were reduced.Myocardial Z lines and myofilaments were more regularly arranged,mitochondrial swelling and autophagy were reduced,and structural damage to the endoplasmic reticulum and Golgi complex was lessened.Conclusion:Qishen Yixin granule may have a delayed effect on myocardial fibrosis in heart failure(HF)by regulating the TGF-β1/Smads signaling pathway.