目的 观察规律运动训练对自发性高血压大鼠(SHR)心脏肥大的影响,探讨运动发挥心脏保护效应的可能机制。方法 30只SHR随机分为高血压运动组(SHR-Ex)和高血压对照组(SHR-C),15只健康Wistar大鼠作为正常血压对照组(NC)。SHR-Ex组大鼠进行8周游泳运动(每天60 min,5 d/周),SHR-C组和NC组在鼠笼内安静饲养。实验后,利用智能无创血压测试仪测量尾动脉血压,超声心动图监测心脏结构与功能,分离左心室并称重,HE和Masson染色分别获取心肌细胞横截面积(CSA)和胶原容积分数(CVF),Western Blot检测胚胎基因和心脏肥大信号途径蛋白表达量。结果 实验过程中,由于拒跑、死亡等原因共剔除7只大鼠,最终纳入38只,其中NC组15只、SHR-C组12只和SHR-Ex组11只。与NC组比较,SHR-C组大鼠出现向心性心脏肥大,心肌纤维化(CVF升高,P<0.05),心钠素(ANF)、肌球蛋白轻链-2(MLC-2)、钙调神经磷酸酶Aβ亚基(CNAβ)、PI3激酶p110α亚基[PI3-K(p110α)]和磷酸化Akt(p-Akt)蛋白表达量上调(P<0.05);与SHR-C组比较,SHR-Ex组发生离心性心脏肥大,心肌纤维化减轻(CVF下降,P<0.05),心功能增强(P<0.05),ANF、MLC-2和CNAβ蛋白表达量下调(P<0.05),PI3-K(p110α)和p-Akt的变化无统计学意义。结论 长期运动训练能够促进SHR由病理性心脏肥大向生理性心脏肥大转变,其机制可能与钙调神经磷酸酶信号途径活性下降有关。
Abstract
Objective To observe the effects of regular exercise training on cardiac hypertrophy in spontaneously hypertensive rats (SHR) and to explore the possible mechanism of exercise-induced cardioprotective effect.Methods Thirty SHRs were randomly divided into hypertension exercise group (SHR-Ex) and hypertension control group (SHR-C), and fifteen healthy Wistar rats were used as normotensive control group (NC). Rats of SHR-Ex group performed swimming training for 8 weeks (60 min per day, 5 days per week), while those of SHR-C and NC groups were kept quiet in a cage. After the experiment, the caudal artery blood pressure was measured by intelligent non-invasive blood pressure tester, the cardiac structure and function were monitored by echocardiography, the left ventricle was separated and weighed, the cross sectional area (CSA) and collagen volume fraction (CVF) of myocardial cells were obtained by HE and Masson staining respectively, and embryo genes and cardiac hypertrophy signal pathway protein expression were determined by Western Blot.Results During the experiment, a total of 7 rats were excluded due to refusal to run, death or other reasons, and finally 38 rats were included, including 15 rats in the NC group, 12 rats in the SHR-C group and 11 rats in the SHR-Ex group. Compared with NC group, SHR-C group rats showed concentric cardiac hypertrophy, myocardial fibrosis (CVF increased, P<0.05), and up-regulated expression of atrial natriuretic factor (ANF), myosin light chain-2(MLC-2), Calcineurin Aβ subunit (CNAβ), PI3 kinase p110 α subunit [PI3-K (p110α)] and phosphorylated Akt (p-Akt) . Compared with SHR-C group, SHR-Ex group showed eccentric cardiac hypertrophy, reduced myocardial fibrosis (CVF decreased, P<0.05) and enhanced cardiac function (P<0.05), the expression levels of ANF, MLC-2 and CNAβ protein expression were down-regulated (P<0.05), and PI3-K(p110α) and p-Akt had no significant change.Conclusions Long-term exercise training can promote the change from pathological cardiac hypertrophy to physiological cardiac hypertrophy in SHR, which may be related with the decline of calcineurin signal pathway activity.
关键词
运动训练 /
自发性高血压大鼠 /
心脏肥大 /
心肌纤维化 /
信号转导通路
Key words
exercise training /
spontaneously hypertensive rats /
cardiac hypertrophy /
myocardial fibrosis /
signal transduction pathway
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基金
武警后勤学院基础研究项目(WHY202107),天津市自然科学基金项目(17JCYBJC27400)
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