AMPK在小鼠运动性和病理性心肌肥大能量代谢中的作用

Effect of AMPK on Energy Metabolism of Mice in Exercise-induced and Pathological Cardiac Hypertrophy

目的:探讨运动性和病理性心肌肥大模型在能量代谢方面的差异及其调控因素。方法:采用游泳训练构建运动性心肌肥大模型,用主动脉弓缩窄术(TAC)构建病理性心肌肥大模型。12周龄雄性C57Bl/6J小鼠随机分为4组:对照组(Control),运动组(Swim),假手术组(Sham),手术组(TAC),每组10只。实验结束,采用二维超声心动图检测小鼠心室壁肥厚程度和心功能;对心肌组织切片进行Masson染色检测心肌组织纤维化程度;比色法检测心肌组织中游离脂肪酸(FFA)和葡萄糖(Glu)含量;应用实时定量PCR(RT-PCR)检测心肌组织AMPK和PPAR-αmRNA的水平。结果:1)游泳运动和TAC手术两种方法均能使小鼠产生明显的心肌肥大。与相应的对照组相比,两种肥大模型的心脏室间隔厚度(IVS)和左室后壁厚度(LVPW)之和均明显升高(P<0.05),心重/体重比值,左心室/胫骨长度比值与相应的对照组相比也都明显增加(P<0.05);TAC组ANP、BNP的mRNA水平比Swim组明显升高(P<0.01),心肌组织纤维化程度比Swim组明显加重。2)与Sham组相比,TAC组心肌中FFA含量明显增高(P<0.05),且显著高于Swim组(P<0.01);而Swim组心肌的Glu含量比Control组明显升高(P<0.05),且高于TAC组(P<0.05)。3)与相应的对照组相比,Swim组AMPK mRNA表达水平明显升高(P<0.05),且显著高于TAC组(P<0.01);TAC组PPAR-αmRNA表达水平明显降低(P<0.05),也明显低于Swim组(P<0.05)。结论:运动能改善肥大心肌的能量代谢,减小"能量代谢胚胎型再演"的程度,其机制可能是通过激活AMPK的表达来进行调控的。

To explore the differences of energy metabolism in exercise-induced and pathological cardiac hypertrophy and its regulation factor.Methods：The exercise-induced cardiac hypertrophy model was made by swim training,and the pathological model was made by transverse aortic constriction（TAC）.12-week-old C57Bl/6J mice were divided randomly into control group,swim group,sham group and TAC group.By the end of experiments,cardiac hypertrophy,contractility were evaluated by echocardiography,and myocardial fibrosis were detected by Masson staining.Myocardial free fatty acid（FFA）and glucose levels were measured by colorimetric detection,AMPK and PPAR-αmRNA expression were detected by real time PCR（RTPCR）.Results：1）Significant cardiac hypertrophy could both produced by swim training and TAC in mice.Compared with corresponding control groups,interventricular septum thickness（IVS）and left ventricular posterior wall thickness（LVPW）of two cardiac hypertrophy models were significantly increased（P〈0.05）,heart weight/body weight ratio,left ventricular weight/tibia length ratio were also increased significantly（P〈0.05）compared with corresponding control groups.ANP and BNP mRNA expression of TAC group were higher than those of swim group obviously（P〈0.01）,and its＇ myocardial fibrosis was significantly heavier than swim group.2）FFA in myocardium of TAC group were significantly increased compared with those of sham（P〈0.05）and swim group（P〈0.01）,Glu in myocardial of swim group were significantly higher than those of control（P〈0.05）and TAC group（P〈0.05）.（3）AMPK mRNA expression levels were significantly increased of swim group compared with93control（P〈0.05）and TAC group（P〈0.01）,while PPAR-αmRNA expression levels of TAC group were significantly lower than those of sham（P〈0.05）and swim group（P〈0.05）.Conclusion：Exercise could improve energy metabolism in cardiac hypertrophy,and reduce energy metabolism embryonic recapitulation through activating of AMPK expression.