CAJ | 학술논문

目的评价二氮嗪后处理对大鼠离体心脏缺血再灌注损伤的影响.方法雄性SD大鼠,体重250～300 g,成功建立Langendorff再灌注模型的64个心脏随机分为4组(n=16):正常对照组(C组)、缺血再灌注组(I/R组)、二氮嗪后处理组(D组)和线粒体ATP敏感性钾通道阻断剂5-羟葵酸+二氮嗪后处理组(5-HD+D组).采用K-H液平衡灌注20 min时,C组继续灌注K-H液70 min;I/R组、D组和5-HD+D组进行心肌缺血40 min,I/R组缺血前灌注4 ℃ ST.Thomas停跳液10 ml/kg;D组再灌注5 min时灌注含50μmol/L二氮嗪的K-H液5 min,然后再灌注20 min;5-HD+D组灌注二氮嗪前灌注含100 μmol/L 5-羟葵酸的K-H液5 min,再灌注20 min.分别于平衡灌注末与再灌注末时取8个心脏,记录心功能指标,然后提取线粒体,测定心肌细胞线粒体膜电位(MMP)、氧自由基(ROS)生成量和呼吸功能指标.结果各组平衡灌注末时各指标差异无统计学意义(P＞0.05).与C组比较,再灌注末时其余3组心功能和线粒体呼吸功能减退,MMP降低,ROS生成量增加(P＜0.05或0.01);与I/R组和5-HD+D组比较,D组心功能和线粒体呼吸功能改善,MMP升高,ROS水平降低(P＜0.01).结论二氮嗪后处理可减轻大鼠心肌缺血再灌注损伤,其机制与开放线粒体ATP敏感性钾通道而改善线粒体功能有关.
목적 평개이담진후처리대대서리체심장결혈재관주손상적영향.방법 웅성SD대서,체중250～300 g,성공건립Langendorff재관주모형적64개심장수궤분위4조(n=16):정상대조조(C조)、결혈재관주조(I/R조)、이담진후처리조(D조)화선립체ATP민감성갑통도조단제5-간규산+이담진후처리조(5-HD+D조).채용K-H액평형관주20 min시,C조계속관주K-H액70 min;I/R조、D조화5-HD+D조진행심기결혈40 min,I/R조결혈전관주4 ℃ ST.Thomas정도액10 ml/kg;D조재관주5 min시관주함50μmol/L이담진적K-H액5 min,연후재관주20 min;5-HD+D조관주이담진전관주함100 μmol/L 5-간규산적K-H액5 min,재관주20 min.분별우평형관주말여재관주말시취8개심장,기록심공능지표,연후제취선립체,측정심기세포선립체막전위(MMP)、양자유기(ROS)생성량화호흡공능지표.결과 각조평형관주말시각지표차이무통계학의의(P＞0.05).여C조비교,재관주말시기여3조심공능화선립체호흡공능감퇴,MMP강저,ROS생성량증가(P＜0.05혹0.01);여I/R조화5-HD+D조비교,D조심공능화선립체호흡공능개선,MMP승고,ROS수평강저(P＜0.01).결론이담진후처리가감경대서심기결혈재관주손상,기궤제여개방선립체ATP민감성갑통도이개선선립체공능유관.
Objective To investigate the effects of diazoxide postconditioning on myocardial ischemiareperfusion (I/R) injury in isolated rat hearts. Methods Male SD rats weighing 250-300 g were anesthetized with intraperitoneal pentobarbital 40 mg/kg. Their hearts were excised and perfused in a Langendorff apparatus with K-H solution saturated with 95% O2-5% CO2 at 37 ℃. Sixty-four isolated rat hearts were randomized into 4 groups after 20 min of equilibration (n = 16 each): group control (group C), group I/R, group diazoxide postconditioning (group D) and group mito-KATP channel blocker 5-hydroxydecanoate (5-HD) + diazoxide postconditioning (group 5-HD + D). Group C received continuous perfusion for another 70 min. In group I/R, D and 5-HD + D, the hearts underwent 40 min of iscbemia followed by 30 min of reperfusion. 4 ℃ ST. Thomas cardioplegic solution was administered prior to ischemia in group I/R. Group D received 5 min of perfusion with K-H solution containing 50μ mol/L diazoxide at 5 min of reperfusion. Group 5-HD + D received 5 min of perfusion with K-H solution containing 50 μmol/L 5-HD before reperfusion with diazoxide. Eight hearts were taken at the end of equilibration and reperfusion and the indexes of cardiac function were recorded. Then the mitochondria were extracted for determination of mitochondrial membrane potential (MMP), reactive oxygen species (ROS) release, and respiratory function indexes. Results Compared with group C, MMP was significantly decreased, ROS release was significantly increased, mitochondrial respiratory function and cardiac function declined at the end of reperfusion in the other three groups ( P ＜ 0.05 or 0.01 ). MMP was significantly increased, ROS release was significantly decreased, mitochondrial respiratory function and cardiac function were improved in group D compared with group I/R and 5-HD + D.Conclusion Diazoxide postconditioning can reduce myocardial I/R injury in rats via the opening of mito-KATPchannels and improving the mitochondrial function.