超声微泡介导Jumonji基因转导治疗慢性心力衰竭Beagle犬的实验研究

Chronic heart failure (CHF)is cardiac dysfunction syndrome caused by various heart disease ,and has the high incidence and mortality . The key for treatment of CHF is to reverse the excessive activation of neuroendocrine and ventricular remodeling. The foreign research report suggests that Jumonji combined with ANP gene, and prevented re-expression of ANP in the myocardial hypertrophy, so as to achieve the development of prevention of CHF. We got the model of canine heart failure induced by rapid ventricular pacing, and transfected pcDNA3.1- jumonji into myocardium which was carried by ultrasound microbubble contrast and disrruptted by ultrasound- triggered microbubble destruction. The aims were to assess safety and effectiveness of ultrasound microbubble mediated gene transfection of jumonji gene transfection , obesrve the effection of ANP level of Jumonji gene regulation on canine cardiac structure and function, hemodynamics, changes of pathological, gene and protein level, metabonomics and electrophysiological, and discuss on jumonji overexpression promoting secretion of ANP and improving myocardial function in CHF. We will provide a new way for treatment of myocardial dysfunction..

慢性心力衰竭（简称心衰)是各种心脏疾病导致心功能不全的一种综合征，其发病率和死亡率高。治疗心衰的关键是逆转神经内分泌的过度激活和心室重构。国外研究报道提示Jumonji可能通过与ANP基因结合，预防ANP在心肌肥大时的再表达，从而达到预防心衰的发展。本课题拟通过快速起搏造成犬心衰后，将携带pcDNA3.1- Jumonji的超声微泡造影剂经导管注入右室，应用诊断超声技术定向转染心肌，评估超声微泡介导基因转染的安全性和有效性，观察Jumonji基因转染调控ANP水平变化对犬心脏形态结构和心功能、血流动力学、组织病理变化、基因及蛋白水平变化、代谢组学变化及电生理改变等的影响，探讨Jumonji过表达增加ANP分泌是否改善心衰时心功能及机制，进而为治疗心肌功能异常提供新的途径。

慢性心力衰竭（简称心衰)是各种心脏疾病导致心功能不全的一种综合征，其发病率和死亡率高。治疗心衰的关键是逆转神经内分泌的过度激活和心室重构。国外研究报道提示Jumonji可能通过与ANP基因结合，预防ANP在心肌肥大时的再表达，从而达到预防心衰的发展。研究方法：雄性犬随机分为3组：假手术组，心衰组，心衰+Jumonji组。建立慢性犬心衰模型后，将携带pcDNA3.1-Jumonji的超声微泡造影剂经导管注入右室，应用诊断超声技术定向转染心肌，观察Jumonji基因转染调控ANP水平变化对犬心脏形态结构和心功能、组织病理变化、基因及蛋白水平变化、代谢组学变化及电生理改变等的影响。与心衰组比较，Jumonji mRNA及蛋白在心衰+Jumonji组犬左心室心肌组织显著增加，ANP水平明显降低，左室舒张末期容积显著减小及EF值显著增加。心衰组犬心肌细胞肌丝溶解,线粒体肿胀,嵴断裂.，心衰+Jumonji组犬肌小节完整,肌丝排列整齐,线粒体结构正常。与心衰组比较，转染Jumonji后心衰+Jumonji组犬血清中内源性代谢物柠檬酸、肌酸、γ－氨基丁酸、乳酸、肉碱、葡萄糖等含量下降，心室肌ERP明显增加。Jumonji过表达减少ANP分泌，纠正心衰时心功能、延长ERP、改善心肌代谢。