rAAV1-SERCA2a转染改善心力衰竭犬心功能及其机制探讨  

Transfection of rAAV1-SERCA2a improves cardiac function of beagles with heart failure

作　　者：米亚非[1] 李小鹰[2] 江建军[1] 付治卿[2] 鲁晓春[2] 

机构地区：[1]温州医科大学附属台州医院心内科,浙江台州317000 [2]解放军总医院老年心血管病一科,北京100853

出　　处：《中国病理生理杂志》2014年第2期208-213,共6页Chinese Journal of Pathophysiology

基　　金：国家重点基础研究发展计划(973计划)(No.2006CB503806)

摘　　要：目的:研究重组1型腺相关病毒(rAAV1)介导的肌浆/内质网Ca2+-ATP酶2a(SERCA2a)基因转移对心力衰竭(HF)犬心功能的作用并探讨其机制。方法:采用快速右心室起搏建立比格犬的HF模型,设对照组、HF组、HF+EGFP组和HF+SERCA2a组(均n=4)。后2组经开胸心肌内注射rAAV1-EGFP或rAAV1-SERCA2a,剂量为1×1012病毒基因组。结果:基因转移30 d后,HF+SERCA2a组超声心动图左室射血分数接近对照组,较HF组明显改善(P<0.05),SERCA2a mRNA较HF组显著提高(P<0.05),SERCA2a蛋白在心肌组织中的表达显著高于HF组(P<0.05),心肌细胞凋亡指数和基质金属蛋白酶9(MMP-9)表达较HF组显著降低(P<0.05)。HF+EGFP组各项观察指标接近HF组。但是,受磷蛋白mRNA的水平没有改变。结论:rAAV1-SERCA2a转染上调HF犬心肌组织SERCA2a的表达,能改善心功能,抑制心室重塑;其机制可能与抑制心肌细胞凋亡、下调MMP-9表达有关。AIM： To study the effects of recombinant adeno-associated virus type 1 （rAAV1）-sarcoplasmic/ endoplasmic reticulum calcium ATPase 2a （SERCA2a） transfection on the cardiac function of beagles with heart failure （HF）. METHODS ： The beagles were used to make an animal model with heart failure after rapid right ventricular pacing （230 beats/min） for 30 d. A reduced rate （180 beats/rain） was continuously applied for another 30 d. The beagles were divided into 4 groups （ n =4） ： control group, HF group, HF ＋ EGFP group and HF ＋ SERCA2a group, rAAV1-EGFP and rAAV1-SERCA2a （both 1 × 10^12 viral genomes） were intramyocardially injected into the animals in the latter 2 groups, re- spectively. RESULTS ： After transfection for 30 d, the left ventricular systolic function in HF ＋ SERCA2a group was simi- lar to that in control group, and significantly higher than that in HF group （P 〈 0.05）. The ratio of SERCA2a mRNA/ GAPDH mRNA was significantly higher in HF ＋ SERCA2a group than that in HF group （P 〈 0.05）. The expression level of SERCA2a in the myocardial tissues was higher in HF ＋ SERCA2a group than that in HF group （P 〈 0.05 ）. The apoptot- ic index of the cardiomyocytes and the protein expression of MMP-9 were much lower in HF ＋ SERCA2a group than those in HF group （P 〈 0.05 ）. No significant difference of all parameters was observed between HF group and HF ＋ EGFP group. The mRNA level of phospholamban was unchanged. CONCLUSION： Transfection of SERCA2a improves the ex- pression of SERCA2a, restores the cardiac function and inhibits left ventricular remodeling by reducing the cardiac cell ap- optosis and the MMP-9 expression in the heart failure beagles.

关 键 词：心力衰竭 快速右心室起搏 肌浆 内质网Ca^2+-ATP酶2a 腺相关病毒 

分 类 号：R541.61[医药卫生—心血管疾病]