TGF-β/TIMP-1/MMP-1信号通路在有氧运动改善心衰大鼠心脏重塑中的作用

关键词：有氧运动  心力衰竭  大鼠  心脏重塑  基质金属蛋白酶  细胞外基质

Keywords:aerobic exercise  heart failure  rats  cardiac remodeling  matrix metalloproteinase  extracellular matrix

摘要：

      摘要 目的：观察10周有氧运动对慢性心力衰竭大鼠心脏重塑的影响并探讨转化生长因子-β/金属蛋白酶组织抑制物-1/基质金属蛋白酶-1（transforming growth factor-β/tissue inhibitors of metalloproteinase-1/matrix metalloproteinase，TGF-β/TIMP-1/MMP-1）信号通路在心衰运动康复中的作用。 方法：38只Wistar大鼠随机分为假手术对照组（S组）、心衰对照组（H组）和心衰运动组（HE组）。HE组大鼠进行10周跑台运动，S组和H组保持安静状态。利用心脏超声检测心脏结构与功能；利用Masson染色法检测心肌胶原容积分数（CVF）；实时荧光定量PCR 检测Ⅰ型胶原（Col-Ⅰ）、Ⅲ型胶原（Col-Ⅲ）和心钠素（ANF）mRNA表达，Western blot检测TGF-β、TIMP-1和MMP-1蛋白表达水平。 结果：①与S组比较，H组左室重量（LVW）、左室质量指数（LVMI）、左室舒张期前壁厚度（LVAWDd）、左室收缩期前壁厚度（LVAWDs）、左室舒张期后壁厚度（LVPWDd）、左室收缩期后壁厚度（LVPWDs），胶原容积分数（CVF），Col-Ⅰ、Col-Ⅲ和心钠素（ANF） mRNA，TGF-β，MMP-1和TIMP-1蛋白表达升高（P<0.05），BW、LVIDd、FS、LVEF，MMP-1/TIMP-1比值降低（P<0.05）。②与H组比较，HE组CVF，Col-Ⅰ、Col-Ⅲ和ANF mRNA，TGF-β、MMP-1和TIMP-1蛋白表达降低（P<0.05），LVW、LVMI、LVIDd，FS、LVEF，MMP-1/TIMP-1比值升高（P<0.05）。 结论：长期运动改善心衰大鼠心脏重塑，其机制与部分恢复TGF-β/TIMP-1/MMP-1信号功能，减少胶原沉积并减轻心肌纤维化有关。

Abstract:

      Abstract Objective: To observe the effects of 10-week aerobic exercise on cardiac remodeling in chronic heart failure rats and investigate the possible role of transforming growth factor-β/tissue inhibitors of metalloproteinase-1/matrix metalloproteinase (TGF-β/TIMP-1/MMPs) signal pathway in exercise rehabilitation of heart failure. Method: A total of 38 Wistar rats were randomly divided into sham operation control (S) group, heart failure control (H) group and heart failure exercise (HE) group. Rats in HE group performed aerobic treadmill exercise of 10 weeks, while those of S and H groups maintained in resting state. Cardiac structure and function parameters were determined by ultrasonic cardiography; heart collagen volume fraction (CVF) was acquired by Masson staining; mRNA expressions of myocardial collagen type Ⅰ(Col-Ⅰ), collagen type Ⅲ(Col-Ⅲ) and atrial natriuretic factor (ANF) were detected by real-time fluorescent quantitation PCR; protein expressions of TGF-β、TIMP-1 and MMP-1 were determined by Western blot technique. Result: ①Compared with rats of S group, HR, left ventricular weight（LVW）, left ventricular mass index（LVMI）（LVMI=LVW/BW）, left ventricular anterior wall diameter at diastole（LVAWDd）, left ventricular anterior wall diameter at systole（LVAWDs）, left ventricular posterior wall diameter at diastole（LVPWDd）, left ventricular posterior wall diameter at systole（LVPWDs）, CVF, mRNA of Col-Ⅰ, Col-Ⅲ and ANF, protein of MMP-1 and TIMP-1 increased (P<0.05) while BW, LVIDd, FS, LVEF, MMP-1/TIMP-1 ratio decreased (P<0.05) in those of HF group.②Compared with animals of HF group, CVF, mRNA of Col-Ⅰ, Col-ⅠII and ANF，protein of TGF-β, MMP-1 and TIMP-1 reduced (P<0.05) while LVW, LVMI, LVIDd, FS, LVEF and MMP-1/TIMP-1 ratio raised (P<0.05) in those of HE group. Conclusion: Long-term aerobic exercise could improve cadiac remodeling in rats of heart failure, which was related to partially restore function of TGF-β/TIMP-1/MMP-1 signal pathway and reduce collagen deposition, alleviate myocardial fibrosis.