抗阻训练促进骨骼肌分泌神经营养因子1和卵泡抑素样因子1对心梗心脏的保护效应

Cardiopathy is one of the most incident and fateful diseases in currently China's urban and rural. The morbidity of myocardial infarction is rising rapidly and showing a significant younger trend, made it become one of the major killers of human health. The relationship of exercise training and the prevention of cardiovascular diseases and the effect of exercise on rehabilitation of cardiovascular diseases have become the focus of research attention. The purpose of this project is to study the protective effect of resistance training on myocardial infarction by promoting secretion or Under-expression of NRG1 and FSTL-1 from skeletal muscle and explore the possible mechanism. New hypothesis for skeletal muscle after exercise protects the myocardial infarction heart.In the present study, animal experiments and research in levels of isolated organs, tissues and cell molecular will be used to confirm the safety and effectiveness of resistance training on myocardial infarction, and determine the effects of resistance training on cardiomyocyte proliferation, apoptosis, and myocardial revascularization in infarcted rats; Lentiviral vectors and experimental studies in vitro or vivo will be used to study the effects of NRG1 and FSTL-1 which released from skeletal muscle during resistance training on myocardial cell proliferation, apoptosis and angiogenesis and explore the possible molecular mechanism. Through these research, this study wants to provide the evidence for protection effects of exercise training on cardiac function improvement and cardiac rehabilitation in myocardial infarction rats.

目前心脏病是我国城乡发病率和死亡率在前三位的疾病之一，心梗发病率迅速上升并呈年轻化趋势，已经成为危害人类健康的主要杀手。运动与心血管疾病预防，心血管疾病的运动康复已经成为关注热点。本项目提出运动刺激骨骼肌内分泌保护MI心脏功能这一新假说，旨在探索抗阻训练促进骨骼肌分泌肌肉因子NRG1和FSTL-1对心梗心脏的保护作用及其机制。本课题拟通过整体动物实验、离体器官、组织细胞和分子水平，确定骨骼肌抗阻训练保护心梗大鼠心功能的安全性和有效性；确定对心梗心肌细胞增殖/凋亡和心肌血管再生的影响；通过慢病毒载体导入和体内外实验，确定抗阻训练促进骨骼肌释放或低表达NRG1和FSTL-1对心肌细胞增殖/凋亡和血管再生的影响；通过细胞培养和在体验证实验,研究NRG和FSTL-1影响心梗心肌细胞增殖/凋亡和血管新生的可能机制。通过探索旨在为运动改善缺血心脏功能和心脏康复提供实验依据。

采用SD大鼠心梗模型和持续/间歇/抗阻/机械振动等运动方式以及外源性rh NRG1、rhFSTL1干预，测定心梗面积和心功能、心肌细胞和血管增殖、离体心肌细胞钙瞬变和收缩功能。检测心肌局部和循环NRG1、FSTL1、LIF、CTRP3水平、PI3K-Akt-Erk1/2、TGFβ- Smad2/3、Wnt/β-catenin、NRG1-PI3K-Akt-eNOS-PKG-PLN-SERCA2a、LIF-LIFR-STAT3、CTRP3/pAkt-VEGF等信号通路。采用斑马鱼心脏特异性NRG1过表达模型，检测心肌细胞增殖、smyd1、hsp90α及murf1、NRG1/ErbB4/Akt信号。采用HUVECs细胞实验，探讨FSTL1刺激小管形成的效果及机制。结果发现，抗阻训练改善MI大鼠心功能具有较高有效性和安全性，可抑制MI致骨骼肌萎缩且具有性别差异；抗阻和间歇运动对NRG1/ErbB2/4和Wnt/β-catenin激活效果更显著。间歇运动显著激活心梗大鼠骨骼肌LIF-LIFR-STAT3信号，增加血清LIF和CTRP3水平，激活心梗心脏LIF-LIFR-STAT3、CTRP3/pAkt-VEGF和NRG1-PI3K-Akt- eNOS-PKG-PLN- SERCA2a信号；抗阻训练显著激活骨骼肌NRG1/ErbB4和PI3K/Akt信号，升高骨骼肌FSTL1水平，激活心肌TGFβ-Smad2/3信号；上调骨骼肌Smyd1表达，抑制MuRF1和Hsp90α表达，改善心梗大鼠骨骼肌萎缩，刺激心肌血管新生、降低心肌纤维化和改善心功能。发表SCI源刊论文4篇，CSSCI期刊论文13篇；举办全国性学术会议1次，参加学术会议7次，培养毕业博士生3名，毕业硕士研究生业9名，获国家留学基金委高水平大学联合培养博士研究生计划项目2项，青年骨干教师项目1项。