尼克地尔后处理对心肌缺血／再灌注损伤的保护作用

Protection of postconditioning with nicorandil on myocardial ischemia/reperfusion injury

目的探讨尼克地尔后处理对心肌缺血/再灌注损伤的保护作用及其机制。方法 26只SD大鼠随机分为3组,盐酸异丙肾上腺素(ISO)组8只,尼克地尔后处理组10只,对照组8只。ISO组和尼克地尔后处理组给予ISO(5 mg/kg)腹腔注射,1次/d,连续3 d;尼克地尔后处理组于注射ISO 1 h后尾静脉注射尼可地尔(1 mg/kg),1次/d,连续3 d;对照组腹腔注射等量生理盐水。三组大鼠于第3天注射后24 h处死,检测血清心肌肌钙蛋白I(cTnI)、钾离子通道蛋白Kir6.2及线粒体电压依赖型阴离子通道(VDAC)、IL-10在心肌组织的表达,并进行Nitrotyrosine免疫组织化学染色。结果尼克地尔后处理组大鼠的血清cTnI低于ISO组,差异有统计学意义(P<0.01);ISO组局部心肌组织Kir6.2表达明显低于对照组,尼克地尔后处理组Kir6.2表达高于对照组;各组间VDAC表达基本一致;ISO组可见大量心肌细胞胞浆表达Nitrotyrosine,对照组和尼克地尔后处理组无表达;尼克地尔后处理组IL-10的表达明显高于ISO组及对照组。结论尼克地尔后处理可减轻心肌缺血/再灌注损伤,其作用机制与开放钾离子通道,抑制自由基的产生,从而抑制炎症反应有关。

Objective To explore the mechanism of protection of postconditioning with nicorandil on myocardial isch- emia/reperfusion （I/R） injury in rats. Methods Twenty-six SD rats were randomly divided into control group （8 rats）, isopro- terenol （ISO）） group （8 rats） and nicorandil postconditioning group （10 rats）. ISO （5mg/kg） was injected intraperitoneally to ISO group and nicorandil postconditioning group once daily for 3 days. For nicorandil group, rats were injected via tail vein with nicorandil （lmg/kg） 1 hour after ISO injection once daily for 3 days. While same amount of physiological saline was injected to control group rats. Rats from 3 groups were sacrificed 24 hours after the 3rd day injection. Serum cardiac troponin I （cTnI） was measured, and the expressions of potassium ion channel protein kir6.2, voltage-dependent anion channel （VDAC） and I1- 10 were detected and stained by nitrotyrosine immunohistochemistry approach. Results Serum cTnl level of nicorandil group was significantly lower than that oflSO group （P〈0.01）. Comparing to control group, the expression of Kir6.2 was significantly lower in ISO group while was higher in nicorandil group. No differences were found in expression of VDAC among these three groups. Big amount of nitrotyrosine was observed in cytoplasm of eardiocytes in ISO group and no nitrotyrosine was found in the other two groups. The expression of I1-10 was significant higher in nicorandil group than that in ISO and control group. Conclusions Nicorandil postconditioning attenuates myocardial ischemia/reperfusion injury, possibly by inhibiting free radi-cals generation and inflammatory response via opening potassium channels.