Anti-apoptotic Potency of TNFR:Fc Gene in Ischemia/Reperfusion-Induced Myocardial Cell Injury
Anti-apoptotic Potency of TNFR:Fc Gene in Ischemia/Reperfusion-Induced Myocardial Cell Injury
复制标题
DOI：
10.1007/s10753-014-9975-1
复制
发表时间：
2015-04-01
期刊：
影响因子：
5.1
通讯作者：
Li, Zi-Cheng
中科院分区：
文献类型：
--
作者：
Guo, Jun;Zheng, Dong;Li, Zi-Cheng
本研究旨在探讨TNFR：Fc基因在缺血再灌注和缺氧再给氧诱导的H9 c2大鼠心肌细胞损伤中的抗凋亡作用。将大鼠随机分为假手术组、rAAV-EGFP治疗组和rAAV-TNFR：Fc治疗组，每组8只。建立大鼠I/R心肌梗死模型后，分别于左室前壁和后壁4个部位注射rAAV-EGFP或rAAV-TNFR：Fc。再灌注72 h后观察TNFR：Fc对心肌细胞凋亡及心功能的影响。在体外研究中，在单独用nomoxia处理或在rAAV-GFP或rAAV-TNFR：Fc存在下用缺氧/复氧处理的H9 c2大鼠心肌细胞中分析细胞凋亡。结果发现：（1）TNFR：Fc基因可改善I/R诱导的AMI后心功能（EF、LVESP、LVEDP和dp/dt（max））;（2）TNFR：Fc基因可抑制I/R诱导的细胞凋亡，降低血清和心肌组织中TNF-α的水平;（3）TNFR：Fc基因可通过抑制caspase-3的活化和Bcl-2/Bax比值正常化来防止缺氧/复氧诱导的H9 c2大鼠心肌细胞凋亡。结论TNFR：Fc基因转染对缺血再灌注心肌细胞损伤具有抗凋亡作用。
The aim of the study was to investigate the anti-apoptotic potency of TNFR:Fc gene in ischemia/reperfusion-induced myocardial cell injury and hypoxia/reoxygenation-induced H9c2 rat cardiomyocytes injury. Rats were randomly divided into the following groups (n = 8): (1) sham operation group; (2) ischemia-reperfusion (I/R) rats treated with rAAV-EGFP; (3) I/R rats treated with rAAV-TNFR:Fc group. rAAV-EGFP or rAAV-TNFR:Fc was injected intra-myocardial at four sites on the anterior and posterior walls of left ventricle immediately after the construction of I/R-induced AMI model in rats. The effects of TNFR:Fc on apoptosis and cardiacfunction were observed after 72 h of coronary reperfusion. In the in vitro study, apoptosis was analyzed in H9c2 rat cardiomyocytes treated either with nomoxia alone, or hypoxia/reoxygenation in the presence of rAAV-GFP or rAAV-TNFR:Fc. We found that (1) TNFR:Fc gene improved cardiac function (EF, LVESP, LVEDP and dp/dt (max)) post I/R-induced AMI; (2) TNFR:Fc gene inhibited I/R-induced apoptosis and attenuated the level of TNF-alpha in serum and cardiac tissue; (3) TNFR:Fc gene prevented apoptosis in hypoxia/reoxygenation-induced H9c2 rat cardiomyocytes associated with inhibition of caspase-3 activation and normalization of ratio of the Bcl-2/Bax. We concluded that TNFR:Fc gene transfection has anti-apoptotic potency in ischemia/reperfusion-induced myocardial cell injury.