跑步训练诱导小鼠生理性心脏肥厚模型

A mouse model of physiological cardiac hypertrophy induced by exercise-training on treadmill

目的用长期跑步训练诱导小鼠的生理性心脏肥厚模型,与主动脉缩窄手术诱导的病理性心脏肥厚模型进行比较。方法 8周龄野生型雄性C57BL/6小鼠分为跑步运动组,正常对照组,手术刺激组和假手术组。运动组跑步训练40d,手术刺激组行主动脉缩窄手术2周,从组织形态学、超声心动图、分子标志物表达等方面对模型进行全面评估。结果运动训练组小鼠心脏体重比与正常对照组相比增加27.2%(P<0.05),左心室体重比增加25.8%(P<0.01),心脏显著肥厚。超声心动图显示,与各自的对照组相比,运动组和手术组小鼠模型的左心室后壁厚度均显著增加(P<0.05),但运动组小鼠的相对室壁厚度无明显变化,而手术组小鼠相对室壁厚度显著增加50%(P<0.05),提示两种不同的心脏肥厚导致在心脏结构改变上差别显著。心脏肥厚分子标志物心房利钠肽和脑钠肽在手术组表达显著上调9.5倍和4.5倍,而在运动组下调为对照组的0.48倍和0.58倍,提示两种不同肥厚的分子机制差别迥异。结论长期跑步运动可以成功的诱导小鼠生理性心脏肥厚模型,其表型和分子机制与手术刺激的病理性肥厚差别显著。

Objective To investigate whether exercise-training on a treadmill can induce physiological cardiac hypertrophy in mice,and to determine the difference between the physiological and pathological cardiac hypertrophy.Methods Forty wild-type male C57BL/6 mice were randomly divided into four groups（10 mice in each group）： normal control,training group,sham control,and transverse aortic constriction（TAC） surgery group.After treadmill training for 40 days and at 2 weeks after TAC surgery,the heart function and structure were evaluated by echocardiography and the molecular hypertrophic-markers were measured by real-time PCR.Results Compared with the untrained littermates,the heart weight/body weight ratio and left ventricular weight/body weight ratio were increased by 27.2% and 25.8% in the trained mice,respectively（P0.05）,indicating that cardiac hypertrophy occurred in the trained group.Although the increase in heart mass was comparable between the training group and surgery group,the heart structure and function were different significantly.The thickness of the left ventricular posterior wall was significantly increased in both the training group and TAC group（P0.05）.The relative wall thickness was significantly increased by 50% in the TAC group but not changed in the training group.The left ventricular ejection fraction was significantly decreased by 13.4% in the TAC group compared with that of the trained group（P = 0.029）,indicating that the heart function was impaired by the effect of chronic pressure overload.The hypertrophic molecular markers ANP and BNP,which were dramatically increased up to 9.5-fold and 4.5-fold in the TAC group,were decreased in the training group.Conclusions Chronic excise-training on treadmill can induce physiological cardiac hypertrophy in mice,which is significantly different from the pathological hypertrophy in heart function,structure and gene expression.