CAJ | 학술논문

目的评价尼可地尔预先给药对兔心肌缺血再灌注时心肌线粒体的影响.方法雄性新西兰白兔32只,随机分为4组(n=8),假手术组(S组)仅在左冠状动脉旋支中点穿线;I/R组、尼可地尔组(N组)和尼可地尔+5-羟葵酸组(N+5-HD组)均进行心肌缺血30 min.N组和N+5-HD组缺血前10 min静脉注射尼可地尔100μg/kg负荷量,随后以10μg·kg-1·min-1的速率静脉输注至缺血前即刻;N+5-HD组在缺血前20 min静脉注射线粒体ATP敏感性K+通道阻断剂5-羟葵酸5 mg/kg.再灌注120 min时,取心肌组织,测定线粒体膜电位、心肌Bcl-2、Bax和细胞色素c(Cyt c)表达水平,计算Bcl-2和Bax表达的比值(Bcl-2/Bax).电镜下观察线粒体超微结构.结果与S组比较,其余3组线粒体膜电位、Bcl-2/Bax降低,Cyt c表达上调(P＜0.05);与I/R组比较,N组线粒体膜电位、Bcl-2/Bax升高,Cyt c表达下调(P＜0.05).N组线粒体损伤程度轻于I/R组.5-羟葵酸可逆转尼可地尔导致的上述改变.结论尼可地尔预先给药可保护线粒体膜电位,减少Cyt c易位至胞浆,从而抑制兔心肌缺血再灌注时细胞凋亡,其机制与开放线粒体ATP敏感性K+通道有关.
목적 평개니가지이예선급약대토심기결혈재관주시심기선립체적영향.방법 웅성신서란백토32지,수궤분위4조(n=8),가수술조(S조)부재좌관상동맥선지중점천선;I/R조、니가지이조(N조)화니가지이+5-간규산조(N+5-HD조)균진행심기결혈30 min.N조화N+5-HD조결혈전10 min정맥주사니가지이100μg/kg부하량,수후이10μg·kg-1·min-1적속솔정맥수주지결혈전즉각;N+5-HD조재결혈전20 min정맥주사선립체ATP민감성K+통도조단제5-간규산5 mg/kg.재관주120 min시,취심기조직,측정선립체막전위、심기Bcl-2、Bax화세포색소c(Cyt c)표체수평,계산Bcl-2화Bax표체적비치(Bcl-2/Bax).전경하관찰선립체초미결구.결과 여S조비교,기여3조선립체막전위、Bcl-2/Bax강저,Cyt c표체상조(P＜0.05);여I/R조비교,N조선립체막전위、Bcl-2/Bax승고,Cyt c표체하조(P＜0.05).N조선립체손상정도경우I/R조.5-간규산가역전니가지이도치적상술개변.결론 니가지이예선급약가보호선립체막전위,감소Cyt c역위지포장,종이억제토심기결혈재관주시세포조망,기궤제여개방선립체ATP민감성K+통도유관.
Objective To investigate the effect of nicorandil pretreatment on myocardial mitochondria in a rabbit model of myocardial ischemia-reperfusion (I/R). Methods Tirty-two healthy male New Zealand white rabbits weighing 2.0-2.5 kg aged 4 months were randomly allocated into 4 groups ( n = 8 each): Ⅰ group sham operation (group S); Ⅱ group I/R; Ⅲ group nicorandil pretreatment (group N) and Ⅳ group nicorandil + 5 hydroxydecanoic acid (group N + 5-HD). Myocardial I/R was induced by 30 min occlusion of left circumflex coronary artery followed by 120 min reperfusion. In group N and N + 5-HD a bolus of nicorandil 100 μg/kg was given iv at 10 min before myocardial ischemia followed by continuous infusion at 10 μg· kg-1 · min-1 until the beginning of myocardial ischemia. In group Ⅳ a bolus of 5-HD 5 mg/kg was injected iv at 20 min before myocardial ischemia.The animals were sacrificed at the end of 120 min reperfusion. The mitochondrial membrane potential was measured by flow cytometry using JC-1 fluorescence probe as indicator. Bcl-2, Bax and cytochrome c protein expression was determined by immuno-histochemistry. Myocardial ultrastructure was examined with transmission electron microscope. Results Red fluovescence intensity indicating normal live cells was significantly higher, the green fluorescence intensity indicating apoptotic cells was lower and red/green fluorescence intensity ratio was higher; the Bcl-2/Bax ratio was significantly higher and cytochrome c protein expression lower in group N than in group I/R.5-HD administration negated the protective effect of nicorandil pretreatment against myocardial I/R injury. Conclusion Nicorandil stabilizes mitochondrial membrane potential, decreases cytochrome c protein releasing, and suppresses mitochondrial apoptotic signal transduction by opening the mito-KATP channels.