过表达endophilin A2减轻异丙肾上腺素诱导的心肌肥大

Over-expression of endophilin A2 attenuates myocardial hypertrophy induced by isoprenaline

目的:研究过表达吞蛋白A2(endophilin A2,Endo A2)对异丙肾上腺素(isoprenaline,ISO)诱导的心肌肥大的影响。方法:取健康雄性SD大鼠随机分为假手术组、Ad-EndoA2组、ISO模型组及ISO+Ad-EndoA2组,其中Ad-EndoA2组和ISO+Ad-EndoA2组于给药前1 d左心室壁注射Ad-EndoA2腺病毒,假手术组和ISO组注射磷酸缓冲盐溶液,然后分别连续7 d皮下注射生理盐水或ISO。7 d后用小动物超声测定心功能指标,然后处死大鼠,收集心脏,以心脏重量指数、HE染色及胚胎基因表达水平评价心肌肥大情况,Western blot法检测自噬相关蛋白LC3和P62的表达。结果:小动物超声结果显示,与假手术组相比,ISO组大鼠处于心肌肥大代偿期(左室收缩期前壁厚度、左室收缩期后壁厚度、射血分数和短轴缩短率升高,左室收缩内径及心输出量下降,均P <0. 05),心脏重量指数、HE染色及RT-qPCR结果也均显示心脏发生了明显肥大(P <0. 05),过表达Endo A2可明显减轻ISO诱导的心肌肥大,改善心功能(P <0. 05)。Western blot结果显示,过表达Endo A2明显逆转ISO引起的自噬水平降低(P <0. 05)。结论:过表达Endo A2可减轻ISO诱导的大鼠心肌肥大,可能与加强自噬有关。

AIM:To examine the effect of endophilin A2(EndoA2)over-expression on myocardial hypertrophy induced by isoprenaline(ISO).METHODS:Healthy male SD rats were divided into4groups,including sham group,Ad-EndoA2group,ISO group and ISO+Ad-EndoA2group.The rats in Ad-EndoA2group and ISO+Ad-EndoA2group were injected with Ad-EndoA2adenovirus into the wall of the left ventricle1d before the administration of normal saline or ISO,while the rats in sham group and ISO group were injected with PBS.Subsequently,normal saline or ISO were subcutaneously injected into the rats for7consecutive days.After7d,small-animal echocardiography was used to detect the cardiac function.The hearts were harvested.The heart weight index,hematoxylin and eosin(HE)staining,and the expression of fetal genes were observed to identify myocardial hypertrophy.The protein expression of LC3and P62was detected by Western blot.RESULTS:The results of small-animal echocardiography showed that the rats in ISO group were in the compensatory period of myocardial hypertrophy compared with sham group,evidenced by increased LVAWs,LVPWs,EF and FS,and decreased LVIDs and CO(P<0.05).In addition,the results of heart weight index,HE staining and RT-qPCR showed that myocardial hypertrophy was induced by ISO successfully(P<0.05).Over-expression of EndoA2inhibited myocardial hypertrophy induced by ISO and improved cardiac function(P<0.05).The results of Western blot showed that EndoA2over-expression obviously reversed the decreased level of autophagy induced by ISO(P<0.05).CONCLUSION:Over-expression of EndoA2may attenuate myocardial hypertrophy induced by ISO due to strengthening autophagy.