二氮嗪对自发性高血压大鼠心功能及心肌ERK和JNK表达的影响

THE EFFECTS OF DIAZOXIDE ON MYOCARDIUM FUNCTION AND THE EXP RESSIONS OF ERK AND JNK IN ISOLATED SPONTANEOUS HYPERTENSION RAT HEARTS

目的:探讨二氮嗪对离体自发性高血压大鼠心脏缺血/再灌注心功能及心肌组织ERK和JNK表达的影响及可能机制。方法:雄性自发性高血压大鼠取心行Langendorff灌流。实验分为5组(n=6/组):对照组(Con)在平衡后继续灌流40min,全心缺血25min,复灌30min。其余各组除全心缺血前处理不同外,余均同对照组。缺血预处理组(IP)2次给予5min缺血+10min复灌,二氮嗪预处理组(DP)给予2次含50μmol·L-1二氮嗪的K-H液10min后给不含二氮嗪的K-H液5min,5-HD、5-HD+DP组则在平衡后给予10min150μmol·L-1线粒体KATP阻断剂5-HD,余同Con及DP组。结果:IP组及DP组复灌末左室发展压、+dP/dtmax和-dP/dtmax的恢复率均高于Con组(P<0.01),但两组左室舒张末期压恢复率低于Con组(P<0.01);5-HD能拮抗二氮嗪引起的心功能指标的改善。复灌末IP、DP及5-HD+DP组ERK表达增加。IP组及DP组心肌的JNK表达低于Con组(P<0.05),5-HD+DP组JNK表达显著高于DP组。结论:二氮嗪预处理对离体自发性高血压大鼠心肌缺血/再灌注损伤有保护作用,此保护作用可能与ERK的表达增加及JNK表达减少有关。

Aim： To investigate the effect of diazoxide preconditioning and the role of ERK and JNK in cellular signaling during diazoxide preconditioning protection in isolated spontaneous hypertension rat（SHR） hearts. Methods： Hearts were isolated from male SHR rats, and perfused on a Langendorff apparatus. Five groups were cosidered（ n = 6）. Con： after 40 min perfusion the hearts were submitted to 25 min ischemia followed by 30 min reperfusion. IP： the hearts were preconditioned with 2 periods of 5 min ischemia and 10 mln reperfusion prior to 25 min ischemia. DP： the hearts were preconditioned with 2 periods of 10 min K-H solution with 50μmol·L^-1 diazoxide and 5 min K-H solution repel＇fusion prior to 25 min ischemla. 5-HD： perfuse with 100μmol·L^-1 5-HD（a special mitochondrial ATP sensitive potassium channel blocker） for 10 min followed by 30 min K-H solution perfuslon before 25 min ischemia. 5-HI） ＋ DP： 100μmol·L^-1 15-HD was given for 10min before diazoxide preconditioning. Results： During repel＇fusion, comparing with Con group, the recoveries of left ventricle developed pressure（LVDP）, ＋ dP/dtmax, -dP/dtmax and left ventricle end diastolic pressure （LVEDP） were improved in IP and DP groups（ P〈0.01 vs Con）. At the end of reperfusion, compared with Con group, the expression of ERK in myocardium were higher in IP and DP groups（P〈0.01 vs Con）, there was no significance between 5-HI） and Con group, but 5-HI） couldn＇t inhibit the expression of ERK induced by diazoxide preconditioning. The expression of JNK in IP and DP groups were decreased（ P 〈 0.05 vs Con）, this effect could been inhibited by 5-HI）. Conclusion： These results indicated that diazoxide preconditioning could mimic ischemic preconditioning, the activation of ERK expression and the declining of JNK expression involved in diazoxide preconditioning in isolated SHR hearts.