有氧运动对慢性心力衰竭大鼠血流动力学、心功能和左室重塑基因表达的影响

Effects of Aerobic Training on Haemodynamics,Cardiac Function and Expression of Left Ventricular Remodeling Genes in Rats with Chronic Heart Failure

目的:探讨有氧运动对慢性心力衰竭(CHF)大鼠血流动力学、心功能和左室重塑基因表达的影响,以及抑制CHF时左室重塑的可能机制。方法:通过结扎雄性大鼠冠状动脉建立心梗后CHF模型,4周后被随机分为假手术组(Sham组)、心衰组(HF组)和心衰运动组(HF+E组)。HF+E组进行10周跑台有氧运动,Sham组和HF组保持静息状态。利用超声心动图检测心脏结构和功能;利用跑台递增负荷力竭运动实验测定大鼠运动耐力;实验后利用左室导管法测定血流动力学参数;利用M asson染色法进行组织病理学观察并计算胶原容积分数(CVF),实时荧光定量PCR检测左室重塑基因——I型胶原(Col-I)、III型胶原(Col-III)、基质金属蛋白酶-1(MMP-1)和金属蛋白酶组织抑制物-1(TIMP-1)mRNA表达量。结果:1与Sham组比较,HF组HR、LVEDP、HW、HW/BW、LVESD、LVEDD、CVF以及Col-I、Col-III、M M P-1和TIM P-1 mRNA表达水平升高(P<0.01),LVSP、±dp/dtm ax、BW、FS、LVEF、力竭时间、力竭距离、最大跑速以及MMP-1/TIMP-1比值显著降低(P<0.01);2与HF组比较,HF+E组LVEDP、LVESD、LVEDD、CVF以及Col-I、Col-III、M M P-1和TIM P-1 mRNA表达水平显著性降低(P<0.01),而LVSP、±dp/dtm ax、FS、LVEF、力竭时间、力竭距离、最大跑速以及MMP-1/TIMP-1比值显著性升高(P<0.01)。结论:1 CHF时发生左室重塑,表现为血流动力学异常、心功能下降,其机制与MMP-1/TIMP-1失衡造成的胶原沉积有关;2 10周跑台运动改善CHF大鼠血流动力学异常、提高心功能,从而抑制左室重塑,其机制与部分恢复MMP-1/TIM P-1平衡,减少胶原沉积有关。

Objectives： To explore the effects of aerobic training on haemodynamics, cardiac function and expression of left ventricular remodeling genes in rats of chronic heart failure （CHF） and investigate the possible mechanism of aerobic exercise induced inhibition of cardiac remodeling of CHF. Methods： CI-IF model was established through ligating coronary artery of male rats. After 4 weeks, they were randomly divided into sham operation control group （Sham）, heart failure control group （HF） and heart failure plus exercise group （HF ＋ E）. Rats in HF ＋ E group performed aerobic treadmill exercise of 10 weeks while those of Sham group and HF group maintained rest. Cardiac structure and function were detected by ultrasoundcardiogram, exercise tolerance by incremental treadmill test, haemodynamic parameters with pressure transducer inserted retrograde in left ventricle; histopathology study and collagen volume fraction （CVF） by Masson staining and remodeling gene mRNA expression of cardiac collagen type I （Col-I）, collagen type III （Col-Ill）, matrix metalloproteinase-1 （ MMP-1 ） and tissue inhibitors of metalloproteinase-1 （ TIMP-1 ） by real-time Q-PCR. Results： （1） Compared with Sham group, HR, LVEDP, HW, HW/BW, LVESD, LVEDD, CVF and mRNA of Col-I, Col-HI, MMP-1 and TIMP-1 significantly increased （ P 〈 0.01 ） while LVSP, ＋ dp/dt^x, BW, FS, LVEF, exhaust time, exhaust distance, maximal speed and MMP-1/ TIMP-1 ratio significantly reduced （P 〈 0.01 ） in HF group; （~） Compared with HF group, LVEDP, LVESD, LVEDD, CVF and mRNA of Col-I, Col-III, MMP-1 and TIMP-1 significantly decreased （P 〈 0. 01 ） while LVSP, ＋ dp/dtm^x, FS, LVEF, exhaust time, exhaust distance, maximal speed and MMP-1/ TIMP-1 ratio increased significantly （ P 〈 0.01 ） in HF ＋ E group. Conclusion： （1） Left ventricular remodeling in CHF represented haemodynamic dysfunction and reduced cardiac function, which was related to the imbalance of MMP-1/TIMP-1 induced collagen deposition; 2） treadmill running exercise of 10 weeks improved haemodynamic dysfunction and enhanced cardiac function, thus inhibiting left ventricular remodeling in rats of CHF, which was partially related to the restored balance of MMP-1/TIMP-1 and reduced collagen deposition.