摘要
[目的]本研究旨在确定通脉养心丸(TM)是否可以进一步缓解心室重构(VR)。探索潜在的机制。[方法]建立大鼠心肌缺血再灌注(I/R)损伤模型后,将大鼠分为7组,分别为对照组、假手术组、I/R组、TM(1 g/kg)组、TM(2 g/kg)组、TM(4 g/kg)组和通心络胶囊(TXL)组。在给药后第3天和第28天进行实验。通过超声检测心脏结构和功能。2,3,5-氯化三苯基四氮唑(TTC)染色观察心肌缺血面积。通过苏木精-伊红染色进行心脏病理学评估。采用全自动生化分析仪和试剂盒分别检测心肌酶活性和氧化活性。Masson染色用于检测胶原化程度。通过ELISA检测炎症和心肌纤维化相关蛋白的表达水平。[结果]给药3天后,TM改善了心脏功能和形态。有效改善I/R大鼠心肌梗死面积,抑制心肌酶的异常活性,显著降低超氧化物歧化酶活性和CRP、TNF-α以及IL-1β蛋白表达。它抑制氧化应激和炎症的爆发,减少心肌病理损伤。给药28天后,TM改善心功能,抑制心室扩张,改善心室壁厚度,显著降低CTGF、MMP-2、MMP-9蛋白表达,降低心肌纤维化程度。[结论]TM可有效缩小梗死面积,改善心脏结构和功能,降低心肌胶原化程度,进一步缓解VR。具体机制涉及早期抑制炎症反应和晚期缓解心肌纤维化。
Objective:This study aimed to determine whether Tongmai Yangxin pills(TM)can attenuate ventricular remodeling(VR)and to explore the underlying mechanisms.Methods:After the myocardial ischemia-reperfusion(I/R)injury model has been established,the rats were divided into seven groups:control,Sham,I/R,TM(1.0 g/kg),TM(2.0 g/kg),TM(4.0 g/kg),and Tongxinluo capsules,respectively.Experimental parameters were assessed on days 3 and 28 after drug administration.Cardiac structure and function were assessed by echocardiography.Myocardial ischemia was quantified using triphenyl tetrazolium chloride staining,and the cardiac pathology was evaluated using hematoxylin-eosin staining.Myocardial enzyme and oxidant activities were detected using an automatic biochemical analyzer and kit,respectively.Masson's trichrome staining was used to analyze the degree of collagen deposition.The expression levels of inflammation and fibrosis-related proteins were detected using enzyme-linked immunosorbent assays.Results:After 3 days of administration,TM improved cardiac function and morphology.It effectively reduced the area of myocardial infarction in I/R rats,inhibited the abnormal activity of myocardial enzymes,and significantly reduced superoxide dismutase activity,as well as C-reactive protein,tumor necrosis factor-α,and interleukin-1βexpression at the protein level.TM administration inhibited oxidative stress,inflammation,and myocardial pathological damage.After 28 d of administration,TM improved heart function;inhibited ventricular dilation and the thinning of the ventricular wall;significantly reduced the protein expression of connective tissue growth factor,matrix metalloproteinase 2,and matrix metalloproteinase 9;and decreased the degree of myocardial fibrosis.Conclusions:TM can effectively reduce the infarct size,improve the cardiac structure and function,reduce myocardial collagen deposition,and attenuate VR.The underlying mechanisms involve the inhibition of inflammatory responses in the early stages and a reduction of myocardial
作者
陈瑞
孟棵
王彩君
吕清波
姜迪
丁鑫亚
徐金鹏
王林
王玉静
周昆
王怡
Rui Chen;Ke Meng;Caijun Wang;Qingbo Lyu;Di Jiang;Xinya Ding;Jinpeng Xu;Lin Wang;Yujing Wang;Kun Zhou;Yi Wang(Institute of Traditional Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin,China;Tianjin Zhongxin Pharmaceutical Group Co.,Ltd.,Le Ren Tang Pharmaceutical Factory,Tianjin,China)
基金
supported by the Graduate Research Innovation Project of Tianjin University of Traditional Chinese Medicine(YJSKC-20191001)
the Graduate Research Innovation Project of Tianjin(JJ1901010302).
关键词
通脉养心丸
心肌缺血再灌注
心室重构
Myocardial ischemia-reperfusion
Tongmai Yangxin pills
Ventricular remodeling
