二氮嗪预处理对自发性高血压大鼠心肌缺血再灌注损伤的影响及机制

Effect and mechanism of diazoxide preconditioning on ischemia/reperfusion injury in the isolated heart of spontaneous hypertension rat

目的 探讨二氮嗪在离体自发性高血压大鼠心脏上模拟缺血预处理效应的可能性及线粒体KATP在其中的作用。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 ) :对照组 (Con)在平衡后继续灌流 4 0min ,全心缺血 2 5min ,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组 ) 2次给予 5min缺血 +10min复灌 ;二氮嗪预处理组 (DP组 )给予 2次含 5 0 μmol·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 10min 15 0 μmol·L- 1 线粒体KATP(mitoKATP)阻断剂 5 -HD ,余同Con组及DP组。结果 IP组及DP组复灌末左室发展压、左心室最大上升速率 (+dP dtmax)和左心室最大下降速率 (-dP dtmax)均高于Con组 (P <0 .0 1) ,但 2组左室舒张末期压低于Con组 (P <0 .0 1) ;5 -HD能拮抗二氮嗪引起的心功能指标的改善。IP组和DP组冠脉流量高于Con组 ,而MDA含量低于Con组 (P <0 .0 1) ,5 -HD组和Con组无差异。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 ,mitoKATP拮抗剂 5

Objective To investigate the effect of diazoxide preconditioning (DP) and the role of mitochondrial ATP-sensitive potassium channels in the preconditioning in isolated spontaneous hypertension rat (SHR) hearts. Methods The hearts isolated from male SHR rats and perfused on Langendorff apparatus were divided into 5 groups (n=6 each). All experiments were started after a 40-min perfusion for equilibration. The control (Con) group was submitted to 25 min of ischemia and 30 min of reperfusion to induce ischemia/reperfusion (I/R) injury. The ischemic preconditioning (IP) group was preconditioned by giving 2 cycles of 5-min ischemia and 10-min reperfusion prior to the I/R procedure. The DP group was preconditioned by giving 2 periods of 10-min K-H solution containing 50 μmol·L -1 diazoxide and 5-min K-H solution reperfusion. The 5-HD group was perfused with 100 μmol·L -1 5-HD (a special mitochondrial ATP sensitive blocker) for 10 min and then with K-H solution for 30 min before the procedure of I/R. The 5-HD+DP group was given 100 μmol·L -1 5-HD for 10min before DP and the procedure of I/R. Results Compared with those in the Con group, the recoveries of left ventricle developed pressure (LVDP), +dP/dt max, -dP/dt max and left ventricle end diastolic pressure (LVEDP) were improved in IP and DP groups (P<0.01). The myocardial content of MDA was lower in IP and DP groups than in the control (P<0.01), but was higher in 5-HT and 5-HD+DP groups than in DP group (P<0.05). Conclusion Diazoxide preconditioning, mimicking the ischemic one, can protect the isolated SHR hearts against I/R injury, and the mitochondrial ATP-sensitive channels are involved in this action.