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二氮嗪对长时程低温保存大鼠心脏Fas/FasL蛋白表达的影响

范莹, 郑鸣之, 郭炜, 蒋建平, 朱立, 沈岳良, 陈莹莹

浙江大学医学院生理系.浙江,杭州 310058；浙江医学高等专科学校药理教研室.浙江,杭州 310053；上海中医药大学病理教研室.上海 201203

摘要

该文旨在研究线粒体ATP敏感性钾（mitochondrial ATP--sensitive potassium channel，mitoK_(ATP)）通道开放剂二氮嗪（diazoxide，DE）对离体长时程低温保存的大鼠心脏促凋亡蛋白Fas和FasL表达的影响。利用Langendorff离体大鼠心脏灌注法，观察心脏在4℃含或不含（对照组）DE的Celsior保存液保存8h后，复灌期心脏作功量（rate--pressure product，RPP）变化情况，采用原位末端标记（TdT--mediated dUTP nick end labeling，TUNEL）染色法检测心肌细胞凋亡和免疫组织化学方法检测Fas和FasL蛋白表达情况。结果显示，在Celsior保存液中加入DE（30#mu#mol／L），复灌期RPP的恢复率在多个复灌时间点上优于对照组；同时可降低长时程低温保存心脏心肌细胞凋亡指数，减少Fas和FasL蛋白的表达。DE的上述作用可被mitoK_(ATP)通道特异性阻断剂5--羟基葵酸盐（5--hydroxydecanoate，5--HD）所取消。以上结果提示，DE可能通过激活mitoK_(ATP)通道来减少Fas和FasL蛋白表达，从而减轻大鼠心肌缺血，再灌注损伤后的心肌细胞凋亡。

关键词： 二氮嗪; Fas/FasL; 线粒体ATP敏感性钾通道; 心脏保存; 心肌保护

Effects of diazoxide on Fas/FasL protein expressions in rat myocardium suffered from long--term hypothermic preservation

Fan Ying, Zheng Mingzhi, Guo Wei, Jiang Jianping, Zhu Li, Shen Yueliang, Chen Yingying

Department of Physiology, School of Medicine, Zhejiang University.Hangzhou 310058,Zhejiang；China；Department of Pathology, Shanghai University of Traditional Chinese Medicine.Shanghai 201203

Abstract

The purpose of this study was to investigate the effect of a mitochondrial ATP-sensitive potassium channel （mitoK_(ATP)） opener, diazoxide （DE）, on Fas/FasL protein expressions in rat heart suffered from long-term hypothermic preservation. The Langendorff isolated rat heart model was used. The hearts were stored in 4℃ Celsior solution with or without （control） DE for 8 h followed by 60 min of reperfusion. The recovery of rate-pressure product （RPP） was observed. Apoptotic cardiomyocytes were detected by TdTmediated dUTP nick end labeling （TUNEL） technique. The expressions of Fas/FasL proteins were also analyzed by immunohistochemical method. The results showed that compared with the control group, DE （30 mmol/L） increased the recovery of RPP during reperfusion, reduced the percentage of apoptotic cells and the expressions of Fas and FasL proteins in rat hearts suffered from 8 h of hypothermic preservation. The above effects of DE were attenuated by a mitoK_(ATP) channel inhibitor 5-hydroxydecanoate （5-HD）. These results indicate that DE could alleviate rat myocardial injury induced by ischemia-repeffusion through reducing the expressions of Fas and FasL proteins via opening of mitoK_(ATP) channel.

Key words: Diazoxide;Fas/FasL;mitochondrial ATP-sensitive potassium channel;heart preservation;cardioprotection

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引用本文：

范莹, 郑鸣之, 郭炜, 蒋建平, 朱立, 沈岳良, 陈莹莹. 二氮嗪对长时程低温保存大鼠心脏Fas/FasL蛋白表达的影响[J]. 生理学报 2008; 60 (1): 11-16.

Fan Ying, Zheng Mingzhi, Guo Wei, Jiang Jianping, Zhu Li, Shen Yueliang, Chen Yingying. Effects of diazoxide on Fas/FasL protein expressions in rat myocardium suffered from long--term hypothermic preservation. Acta Physiol Sin 2008; 60 (1): 11-16 (in Chinese with English abstract).