二氮嗪对长时程低温保存大鼠心脏Fas／FasL蛋白表达的影响  

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

作　　者：范莹[1] 郑鸣之[2] 郭炜[3] 蒋建平[2] 朱立[1] 沈岳良[1] 陈莹莹[1] 

机构地区：[1]浙江大学医学院生理系,杭州310058 [2]浙江医学高等专科学校药理教研室,杭州310053 [3]上海中医药大学病理教研室,上海201203

出　　处：《生理学报》2008年第1期11-16,共6页Acta Physiologica Sinica

基　　金：supported by the National Natural Science Foundation of China (No. 30470635);the Science Foundation ofZhejiang Medical College (No. 2006XZ04)

摘　　要：本文旨在研究线粒体ATP敏感性钾(mitochondrial ATP-sensitive potassium channel, mitoKATP)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 oC 含或不含(对照组) DE 的Celsior 保存液保存8 h 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 μmol/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 mitoKATP 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 mitoKATP 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。The purpose of this study was to investigate the effect of a mitochondrial ATP-sensitive potassium channel （mitoKATP） 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 mitoKATP 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 mitoKATP channel.

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 

分 类 号：R96[医药卫生—药理学]