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促红细胞生成素对大鼠心肌缺血再灌注损伤的保护性作用

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目的:研究促红细胞生成素(EPO)缺血后给药对在体大鼠心肌缺血再灌注损伤的保护作用,并对其机制进行初步探讨.方法:以左冠状动脉前降支穿线结扎法制备SD大鼠心肌缺血模型,松开结扎线造成再灌注.将大鼠随机分成假手术(SHAM)组、缺血再灌注(IR)组、促红细胞生成素(EPO)组和促红细胞生成素+磷脂酰肌醇-3-激酶(PDK)/Akt途径的高选择性阻断剂LY294002(EPO+LY)组.观察心电图Ⅱ导联心律失常发生情况;电镜观察心肌细胞超微结构;以TUNEL法检测细胞凋亡;RT-PCR测定bcl-2,bax及caspase3mRNA含量.结果:EPO组心肌细胞超微结构损伤较轻,细胞凋亡减少,再灌注心律失常发生率降低,bax及caspme-3 mR-NA降低,bcl-2 mRNA增高.结论:EPO对大鼠心肌缺血再灌注损伤具保护作用,LY294002可以减弱EPO的作用,其作用机制与抑制心肌细胞的凋亡作用有关,PDK/Akt通路参与了其信号转导.
Protection of erythropoietin on myocardial ischemia reperfusion injury in rats
AIM:To explore the effect of erythropoietin (EPO) on myocardial ischemia reperfusion injury in rats, discuss the mechanism involved. METHODS: Thirty-five SD rats were randomly divided into 4 groups: Sham operation group (group SHAM), and 3 experimental groups (group IR, group EPO and group EPO + LY). The ischemia repersusion heart model was established by ligating the left anterior descending branch of coronary artery; EPO was administrated by intravenous between ischemia and reperfusion. The occurrence of arrhythmia in electrocardiogram of lead Ⅱ was observed. The change of cardiac ultrastructure were examed by transmission electron microscope. Myocardium cells apoptosis were estimated by TUNEL; bcl-2, bax and caspase3 mRNA transcription were detected by RT-PCR. RESULTS: EPO could lighten the destruction of cardic ultrastructure, lighten reperfusion arrhythmia; EPO could up-regulate the mRNA transcription of bcl-2, and down-regulate the mRNA transcription of bax and caspase-3, inhibit the apoptosis myocardium cells; LY294002 attenuated the effect of EPO. CONCLUSION: EPO could attenuate myocardial ischemia-reperfusion injury. The cardioprotection by EPO required the PI3K pathway.

erythropoietinischemia-reperfusion injuryapoptosis

吴锦波、吴平生、张宏斌、王月刚

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南方医科大学南方医院心内科,广东,广州,510515

广州军区广州总医院医学实验科,广东,广州,510010

促红细胞生成素 缺血再灌注损伤 细胞凋亡

2009

第四军医大学学报
第四军医大学

第四军医大学学报

CSTPCDCSCD北大核心
影响因子:0.599
ISSN:1000-2790
年,卷(期):2009.30(19)
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