慢病毒介导的RNA干扰对醛固酮过负荷心肌梗死大鼠心脏重构的影响  

Lentiviral-mediated RNA interference attenuates cardiac remodeling of myocardial infarction rats in aldosterone overload rats

作　　者：梁远红[1] 周燕[2] 刘烈[1] 陈东骊[1] 陈泗林[1] 林曙光[1] 

机构地区：[1]广东省人民医院心内科广东省医学科学院广东省心血管病研究所,广州510080 [2]武汉大学人民医院急诊科

出　　处：《中华实验外科杂志》2013年第10期2120-2122,共3页Chinese Journal of Experimental Surgery

基　　金：中国博士后科学基金资助项目（20060400780）;广东省医学科研基金资助项目（A2007022）;广东省自然科学基金资助项目（7001120）;湖北省自然科学基金资助项目（2010CDB06806）

摘　　要：目的 观察慢病毒介导的p38丝裂原活化蛋白激酶（p38MAPK）短发夹RNA（PGLV-shRNA）对醛固酮过负荷大鼠心肌梗死后心脏重构的影响并探讨其机制.方法 制作醛固酮过负荷大鼠心肌梗死模型（左室射血分数48.63±6.43）,构建PGLV-shRNA经尾静脉注射,超声评价心脏重构,检测心肌胶原容积分数（CVF）、p38 MAPK、结缔组织生长因子（CTGF） mRNA及蛋白的表达.结果 醛固酮过负荷大鼠心肌梗死后心脏收缩功能显著降低（48.63±6.43比64.62 ±7.90；P＜0.01）,伴CVF增加,p38MAPK、CTGF蛋白表达显著上调（P＜0.01）.PGLV-shRNA明显改善心肌梗死后的心脏重构,减少CVF（36.55 ±6.31比58.62±7.60；P＜0.05）、p38MAPK mRNA和蛋白、CTGF mRNA和蛋白表达（0.42±0.06比0.60 ±0.12；P＜0.05）.结论 醛固酮过负荷大鼠心肌梗死后心脏重构与p38MAPK信号通路介导的心肌细胞纤维化相关,PGLV-shRNA抑制心肌细胞纤维化,改善心肌梗死后的心脏重构.Objective To explore the effects of p38 mitogen-activated protein kinase （p38MAPK）short hair RNA （shRNA） delivered by lentiviral vectors （PGLV） on cardiac remodeling after myocardial infarction （MI） in aldosterone overload rats.Methods The PGLV-shRNA was constructed and injected in aldosterone overload MI rats （LVEF：48.63 ± 6.43）.The cardiac remodeling was measured by cardiac ultrasound and fibrosis was assessed by collagen volume fraction （CVF）.The mRNA and protein expression of p38MAPK and connective tissue growth factor （CTGF） was detected by using reverse transcriptase polymerase chain reaction （RT-PCR） and Western blotting.Results Cardiac systolic function was significantly reduced [（48.63 ±6.43 vs.64.62 ±7.90,P ＜0.01）] in aldosterone overload MI rats,and along with the increases in myocardial fibrosis,p38MAPK and CTGF mRNA and protein expression significantly raised （P ＜ 0.01）.PGLV-shRNA significantly improved the cardiac function,reduced CVF （36.55.35 ± 6.31 vs.58.62 ± 7.60,P ＜ 0.05）,p38MAPK mRNA and protein,and CTGF expression （0.42 ± 0.06 vs.0.60 ± 0.12,P ＜ 0.05）.Conclusion Cardiac function aggravation and remodeling in aldosterone overload MI rats were associated with p38MAPK-mediated myocardial fibrosis.PGLV-shRNA may inhibit cardiac fibrosis and improve post-MI cardiac remodeling.

关 键 词：P38丝裂原活化蛋白激酶 慢病毒 心脏重构 RNA干扰 

分 类 号：R542.22[医药卫生—心血管疾病]