Anti-apoptotic Potency of TNFR:Fc Gene in Ischemia/Reperfusion-Induced Myocardial Cell Injury

作者：Guo, Jun^*; Zheng, Dong; Li, Hai-Rui; Zhang, Ai-Dong; Li, Zi-Cheng

来源：Inflammation, 2015, 38(2): 664-671.

DOI：10.1007/s10753-014-9975-1

• tumor necrosis factor
• apoptosis
• myocytes
• ischemia
• reperfusion
• hypoxia
• reoxygenation

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 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.

• 出版日期2015-4
• 单位暨南大学