摘要
目的:对比研究心肌肌膜和线粒体ATP敏感性钾通道(KA+TP)在缺血预适应(IP)对小鼠体外心脏缺血/再灌注(I/R)损伤后梗死范围、心律失常和心功能的影响。方法:采用改良的Langendorff小鼠心脏灌注系统同步记录C57BL/6小鼠心脏心电图、左心室发展压和左心室压发展速率。选用特异性心肌肌膜KA+TP阻断剂HMR109830μmol/L和特异性心肌线粒体KA+TP阻断剂5HD500μmol/L。分对照组、IP组、IP加HMR1098组和IP加5HD组。IP组稳定16min后,行2个循环的IP,缺血2min和再灌注5min;然后缺血20min和再灌注45min,对照组无IP。在45min再灌注结束后,测定心肌梗死范围。结果:与对照组相比,IP组能显著降低心肌梗死范围,分别为(38·1±1·82)%和(29·4±2·71)%(P<0·05),但对心律失常积分和心功能恢复无明显影响。与IP组相比,IP加HMR1098组和IP加5HD组能显著增加心肌梗死范围和降低心功能,心肌梗死范围分别为(45·6±4·7)%和(51·1±5·2)%,但2组间差异无统计学意义。结论:IP对小鼠体外心脏I/R损伤具有保护作用,心肌肌膜和线粒体KA+TP在IP后I/R损伤过程中均起重要作用。心肌梗死范围可作为IP保护心肌的可靠指标,但要慎重对待心律失常和心功能的变化。
Objective： To compare the role between sarcolemmal and mitochondrial ATP-sensitive K＋ （KATP^＋） channels in ischemic precondition related cardioprotection against global ischemia/reperfusion （GI/R） injury in isolated mouse heart. Method：We measured ECG and left ventricular function in Langendorff-perfused hearts during and after GI/R （GI 20 min/R 45 min） preceded by 2 episodes of ischemic preconditioning （IP, 2 min） separated by reperfusion （5 min）. Sarcolemmal KATP^＋ channel blocker HMR1098 （30 μmol/L） and mitochondral KATP^＋ channel blocker 5-hydroxydecanoate （5HD, 500 μmol/L） were included in the perfusing solution for some experiments. Thirty-two mice were divided into 4 groups with 8 mice （4 males and 4 females） in each group： control, IP, IP＋ HMR1098 and IP＋SHD. Infarct size was measured at the end of reperfuson by 10% triphenyl-tetrazolium cholide （TTC） staining and presented as the percentage of risk area. Result： Infarct size was significantly reduced in IP group （ [29.4 ± 2.71 ] % ） when compared with non-preconditioned control hearts （ [ 38.1 ± 1.82] %, P 〈0.05） after sustained I/R, but there were no differences in recovery of left ventricular （LV） developed pressure between control and IP hearts. HMR1098 and 5HD increased infract size to an equal level （[45.6±4.7]% and [51. 1±5.2] %, respectively） compared to IP group. Conclusion：Our study strongly suggests that IP plays a pivotal role in reducing myocardial infarct size after ischemia/reperfusion injury. However, this pathway does not rescue GI/R mechanical dysfunction. In addition, both sarcolemmal KATP^＋ and mitochondrial KATP^＋ channel are important for the protective role of IP against GI/R injury.
出处
《临床心血管病杂志》
CAS
CSCD
北大核心
2006年第9期532-535,共4页
Journal of Clinical Cardiology
基金
教育部留学人员科研启动基金
教外司留[(No:2001)345号]
