【摘要】 目的本研究拟采用心肌肥厚动物模型来探讨自噬相关蛋白Beclin1在心肌肥厚中的表达以及意义。方法选用20只WT小鼠,完全随机化分为两组:一组为实验组(皮下置入微量泵,异丙肾上腺素ISO 30μg/(g·d),n=10),一组为对照组(假手术组,微量泵,0.9%Na Cl,n=10)。分别在实验开始时与4周时,对各组小鼠进行超声心动图学检测,包括:LVPWd、LVPWs、IVS、FS、LVEF、Vcfc。并且在第4周末处死小鼠,获得体重、组织质量,并取心脏组织进行HE和Masson染色,进行心脏间质纤维化的分析与评价。并取左室心肌组织进行自噬相关蛋白Beclin1的免疫组化检测,分析自噬在心肌重塑中的作用和意义。结果 1微量泵入去甲肾上腺素(ISO)4周后,小鼠的心脏组织代偿性增生,心脏体重指数实验组较对照组明显增加(P<0.001),心脏彩超的结果显示LVPWd、LVPWs、FS、LVEF、Vcfc实验组较对照组明显增加(P均<0.001),进一步提示其为心功能正常心肌肥厚模型。Masson染色结果显示心肌组织发生明显的纤维化。2自噬相关蛋白Beclin1在实验组小鼠心肌纤维化区的表达较对照组心脏组织中的表达明显降低。结论通过置入微量泵体内缓慢输注异丙肾上腺素可以在较短时间内成功建立心肌肥厚模型,而自噬相关蛋白Beclin1表达下调可能是心肌细胞应对ISO输注引起的心肌肥厚的保护性反应,利于心肌细胞的存活。更多还原

【Abstract】 Objective To explore the expression of Beclin1 in myocardiac hypertrophy animal model and its significance. Methods Male wild-type mice were randomized into two groups:experiment group and control group. The mice in experiment group were injected with ISO constantly in four weeks through a micropump,which was placed in the back hypodermal by operation,while the mice in control group were given 0. 9% Na Cl by the same technique. The body weight,tissue weight and echocardiograpgy were recorded at 4week,and left ventricular posterior wall thickness diastolic( LVPWd),left ventricular posterior wall thickness systolic( LVPWs),fiber fractional shortening( FS),left ventricular ejection fraction( LVEF) and rate-corrected velocity of LV fiber shortening( Vc Fc) were measured by echocardiography. The morphology of cardiac myocyte and the degree of cardiac fibrillogenesis were observed by hematoxylin-eosin and Masson staining. The expression of Beclin1 was detected by immunochemistry. Results 1 The heart weight / body weight in experiment group was higher than in control group( P < 0. 001). Cardiac fibrillogenesis was found by hematoxylin-eosin and masson staining in experiment group. LVPWd,LVPWs,interventricular septal thickness( IVS),FS,LVEF,Vcfc in experiment group were significantly higher than those in control group( P < 0. 001). The fibrillogenesis mice with normal cardiac function was established successfully. 2Autophage related protein Beclin1 expression was significantly lower in myocardial tissue in experiment group than in control group. Conclusion Cardiac hypertrophy with normal cardiac function can be successfully stimulated by implanting micropump in vivo which releases constantly ISO. The down-regulation of autophage related protein Beclin1 expression in myocardial hypertrophy may be a protective response to hemodynamic changes induced by ISO and make myocardial cell survive.更多还原