SERCA2a基因治疗慢性心力衰竭的研究进展  

Advances in SERCA2a gene therapy for chronic heart failure

作　　者：宋淑玲 石蕊 SONG Shu-ling;SHI Rui(Department of Thoracic Surgery,Characteristic Medical Center of PAP,Tianjin 300162,China)

机构地区：[1]武警特色医学中心胸心外科

出　　处：《武警后勤学院学报（医学版）》2019年第6期63-69,共7页Journal of Logistics University of PAP（Medical Sciences）

摘　　要：慢性心力衰竭(chronic heart failure,CHF)是心血管疾病的主要原因之一,也是65岁以上老年人住院的主要原因,据估计,目前全世界每年治疗心力衰竭的医疗费用将近千亿美元,因此找到可以延缓和逆转CHF进展的治疗方法是临床研究方向之一。心力衰竭过程中心肌Ca^2+的调节出现严重异常,是导致心力衰竭的一个非常重要的病理原因,也是CHF的一个重要特征。正常心肌细胞内Ca^2+的浓度受到严格调控,可有效控制心肌收缩和舒张功能。在调控心肌细胞内Ca^2+信号的调控网络的许多细胞表面蛋白和胞内细胞器中,肌浆网/内质网Ca^2+-ATP酶-2a(sarco/endoplasmic reticulum Ca^2+-ATPase type 2a,SERCA2a)在心肌Ca^2+调控中起着十分重要的作用。SERCA2a可以将胞浆中的Ca^2+摄入到肌浆网中,使胞浆中Ca^2+水平下降,使肌动蛋白-肌球蛋白解偶联,从而实现心室舒张。越来越多的证据表明SERCA2a在CHF中的表达下调,进而导致严重的收缩和舒张功能障碍。因此,恢复SERCA2a的表达,改善和恢复心肌细胞对Ca^2+的调控能力,为目前研究治疗CHF提供一种很好的选择。随着科技的进步,安全有效的基因传递技术的进步已经让SERCA2a基因治疗作为CHF患者潜在的选择之一。因此,现对SERCA2a基因治疗进行综述,从最开始的质粒模型和动物模型,到后来在CHF患者中的临床试验进展,为临床研究提供参考。Chronic heart failure(CHF)is a major cause of cardiovascular diseases and the leading cause of hospitalization for those over the age of 65,which is estimated to account for nearly 100 billion dollars a year in healthcare costs at present.The successful therapies for delaying and reversing CHF progression are required.One strategy is to recover dysregulated myocardial Ca^2+,a mark of CHF.It is well established that intracellular Ca^2+ concentrations are tightly regulated to control efficient myocardial systolic contraction and diastolic relaxation.Among the many cell surface proteins and intracellular organelles that act as the regulatory network controlling intracellular Ca^2+ signals in cardiomyocytes,sarco/endoplasmic reticulum Ca^2+ ATPase type 2 a(SERCA2 a)plays an important role.SERCA2a is responsible for collecting cytosolic Ca^2+ back into the sarcoplasmic reticulum during diastole,allowing for efficient uncoupling of actin-myosin and subsequent ventricular relaxation.More evidence has demonstrated that the expression of SERCA2a is downregulated in CHF,which contributes to severe systolic and diastolic dysfunction.Therefore,recovering SERCA2a expression and improving cardiomyocyte Ca^2+ level provide an excellent alternative in the treatment of CHF.In fact,advancements in safe and effective gene delivery techniques have led to the emergence of SERCA2a gene therapy as a potential therapeutic choice for CHF patients.This review detailed the progression of SERCA2a gene therapy from plasmid models and animal models to clinical trials in CHF patients,in order to provide a potential way for clinical work.

关 键 词：肌浆网/内质网Ca2+-ATP酶-2a 慢性心力衰竭 基因传递技术 基因治疗 

分 类 号：R541.6[医药卫生—心血管疾病]