有氧运动抑制心梗后心力衰竭大鼠左室重塑及交感神经重塑

摘要

[ ABSTRACT] AIM:To investigate the effects of long-term aerobic exercise on the heart and sympathetic neural remodeling ( structure and function remodeling) in heart failure rats induced by myocardial infarction.METHODS:Heart failure model after myocardial infarction was performed by ligating anterior descending coronary artery in the Wistar rats. Four weeks after operation, the rats were randomly divided into sham operation sedentary ( S) group, heart failure sedenta-ry ( H) group and heart failure exercise ( HE) group.The animals in HE group underwent 10-week treadmill running, while those in S group and H group were sustained in a resting state.The cardiac structure and function including left ven-tricular internal diameter at diastole ( LVIDd) , left ventricular internal diameter at systole ( LVIDs) , left ventricular anteri- or wall diameter at diastole (LVAWDd), left ventricular anterior wall diameter at systole (LVAWDs), left ventricular pos-terior wall diameter at diastole ( LVPWDd) and left ventricular posterior wall diameter at systole ( LVPWDs) , and cardiac function parameters including fractional shortening (FS) and left ventricular ejection fraction (LVEF) were measured by echocardiography.The myocardium was collected for histopathological observation with Masson staining, and the collagen volume fraction ( CVF) was determined.The concentrations of norepinephrine ( NE) in the myocardium and plasma were measured by high-pressure liquid chromatography.The frequency domain analysis was applied for determining the heart rate variability (HRV) via subcutaneous recording electrode involving total power (TP), normalized low power (LFn), nor-malized high power ( HFn) and LF/HF ratio.The mRNA expression of collagen type I ( Col-I) , collagen type III ( Col-III) , atrial natriuretic factor ( ANF) ,α-myosin heavy chain (α-MHC) ,β-myosin heavy chain (β-MHC) , sarcoplasmic endoplasmic reticulum Ca2+-ATPase (SERCA2a) was detected by real-time PCR.The protein levels of nerve growth factor (NGF) and its receptor (TrkA), and tyrosine hydroxylase (TH) were measured by Western blotting.RESULTS:(1) Compared with S group, body weight ( BW) , LVIDd, FS, LVEF, TP, HFn, the mRNA expression ofα-MHC and SER-CA2a, and the protein levels of NGF, TrkA and TH decreased (P<0.05).Left ventricular weight (LVW), left ventricu-lar mass index (LVMI), LVAWDd, LVAWDs, LVPWDd, LVPWDs, CVF, plasma and myocardial NE content, LFn, LF/HF, and the mRNA expression of ANF,β-MHC, Col-I and Col-III increased ( P<0.05) in H group.(2) Compared with H group, LVW, LVMI, LVIDd, FS, LVEF, TP, HFn, the mRNA expression ofα-MHC and SERCA2a, and the pro-tein levels of NGF, TrkA and TH were raised (P<0.05), while CVF, plasma and myocardial NE content, LFn, LF/HF, and the mRNA expression of ANF, β-MHC, Col-I and Col-III decreased ( P<0.05 ) in HE group.CONCLUSION:Long-term aerobic exercise training leads to inhibition of heart and sympathetic neural remodeling and improvement of cardi-ac function and autonomic modulation in the rats after myocardial infarction.%目的：探讨长期有氧运动对心梗后心力衰竭（心衰）大鼠模型左心室及交感神经重塑（结构重塑与功能重塑）的影响，为心衰的机制研究及康复治疗提供科学依据和有效方法。方法：健康雄性Wistar大鼠通过结扎冠状动脉前降支建立心梗后心衰模型，术后4周随机分为假手术安静组（S组）、心衰安静组（H组）和心衰运动组（ HE组）。 HE组进行10周跑台训练，S组和H组保持安静状态。超声心动术检测心脏结构与功能，即左室舒张期内径（ LVIDd）、左室收缩期内径（ LVIDs）、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）、缩短分数（FS）和左室射血分数（LVEF）；Masson染色进行心脏组织病理学观察并获得心肌胶原容积分数（ CVF ）；高压液相色谱法检测心肌和血浆去甲肾上腺素（ NE）水平；经皮下引导电极连续采集心电信号，对自主神经功能参数———心率变异性（ HRV）进行频域分析，包括总功率谱（ TP）、归一化低频功率谱（ LFn）、归一化高频功率谱（ HFn）和LF／HF比值；实时荧光定量PCR检测心肌I型胶原（ Col－I）、III型胶原（ Col－III）、心房钠尿因子（ ANF）、α－肌球蛋白重链（α－MHC）、β－肌球蛋白重链（β－MHC）和肌质网Ca2＋－ATP酶（ SERCA2a） mRNA表达，Western blotting法检测心肌神经生长因子（ NGF）及其受体（ TrkA）和酪氨酸羟化酶（ TH）蛋白表达。结果：（1）与S组比较，H组体重（ BW）、LVIDd、FS、LVEF、TP、HFn、α－MHC和SER－CA2a的mRNA，NGF、TrkA和TH的蛋白表达降低（ P＜0．05）；左室重量（ LVW）、左室质量指数（ LVMI）、LVAWDd、LVAWDs、LVPWDd、LVPWDs、CVF、血浆和心肌NE含量、LFn、LF／HF、ANF、β－MHC、Col－I和Col－III的 mRNA表达升高（P＜0．05）。（2）与H组比较，HE组LVW、LVMI、LVIDd、FS、LVEF、TP、HFn、α－MHC和SERCA2a的 mRNA， NGF、TrkA和TH的蛋白表达升高（P＜0．05）；CVF、血浆和心肌NE含量、LFn、LF／HF、ANF、β－MHC、Col－I和Col－III的mRNA表达降低（P＜0．05）。结论：长期有氧运动可抑制心梗后心衰大鼠左室重塑与交感神经重塑，心功能和自主调节改善。