抗阻训练对心梗大鼠心肌Neuregulin-1的表征和心脏结构与功能的影响

摘要

目的：探讨抗阻训练对心梗（Myocardial Infarction ，MI）大鼠心肌组织中神经调节蛋白（Neuregulin-1，NRG1）及其信号通路表达的影响及其对心脏结构与功能的保护效应。方法：3月龄雄性SD大鼠，体重180～220 g ，随机分为假手术组（Sham ）、心梗组（MI ）和心梗抗阻训练组（MR），每组10只。MI和MR组结扎左冠脉前降支（LAD），建立 MI模型。其中 MR组于术后1周进行为期4周的抗阻训练，结束后测定心功能；采用石蜡切片和 HE、Masson染色技术观察并计算组织形态学变化和胶原容积分数（Collagen volume fraction ，CVF ），采用免疫组化、Real Time-qPCR和Western Blotting 技术检测心肌血管新生、细胞凋亡等相关蛋白α-SMA、CD105、BCL-2和Bax以及NRG1及其受体ErbB2/4和下游信号通路蛋白的表达变化。结果：抗阻训练有效提升了 MI大鼠心功能，改善心肌细胞病理性肥大；促进非梗死区心肌α-SMA和CD105表达、显著升高BCL-2/Bax 比值；显著增加 MI大鼠心肌 NRG1蛋白的表达和erbb2 mRNA表达，升高 PI3K-Akt和ERK1/2的磷酸化水平。结论：本研究发现，抗阻训练可改善 MI心脏的病理性重塑，促进非梗死区血管新生，抑制心肌细胞凋亡，安全有效的改善 MI心脏的功能；抗阻训练可促进心肌 NRG1及其 ErbBs的表达，其心脏的保护效应与心肌NRG1/ErbBs及PI3K/Akt和ERK1/2信号通路激活有关。%Objectives :To discuss the influence of resistance training on cardiac structure and function ,expression of Neuregulin-1(NRG1) and its signaling pathway in rats with myocardial infarction (MI) .Methods :Adult male sprague-dawley rats ,3-mouth old ,weight about 180-220g were randomly divided into three groups :Sham-operated group (Sham ) ,sedentary MI group (MI) and MI with resistance training group (MR) .The MI model in rat was estab-lished by ligation of the left anterior descending (LAD) coronary artery ,and rats in MR were subjected to 4-week resistance training .At the end of the 4-week training ,hemodynamic meas-urement was preformed to evaluate cardiac function ;after that the heart was picked for histo-logical section .The expression levels of α-SMA ,CD105 ,BCL-2 ,Bax ,NRG1 ,ErbB2 ,ErbB4 , PI3K ,Akt and ERK1/2 were detected by Immunohistochemical measurement ,Western Blot-ting or RT-qPCR .Results :Compared with MI group ,resistance training has effectively promo-ted cardiac function and the pathological myocardial hypertrophy ,increased BCL-2/Bax ratio and the expression of α-SMA ,CD105 ,NRG1 protein and erbb2 ,erbb4 mRNA in myocardial tissue ,upregulated the phosphorylation levels of PI 3K-Akt and ERK1/2 signal .Conclusion :Resistance training could improve the cardiac function by ameliorating cardiomyocyte pathologic hypertrophy ,inhibiting apoptosis and promoting angiogenesis after MI ,its mechanism may be associated with NRG1 and the activation of its downstream signaling pathways .