摘要
目的观察JNK丝裂原活化蛋白激酶(MAPK)特异性阻断剂SP600125对大鼠心脏缺血/再灌注(I/R)损伤后心肌梗死面积和收缩功能的影响,探讨阻断该信号转导通路减轻梗死面积及心功能I/R损伤的作用及机制。方法30只健康成年SD大鼠被随机分成5组,每组6只。用穿线结扎冠状动脉前降支(LAD)30min、复灌180min造成心肌I/R损伤动物模型。SP6001253个剂量组在松开结扎前5min和再灌注过程中分次静脉给予SP600125总剂量分别为4.7,14.4,47.9mg/kg;假手术组、模型组相同时间给予等量生理盐水。观察左心室收缩压(LVSP)、左心室等容期压力最大变化速率(±dp/dtmax)和左心室发展压(LVDP′)等血流动力学指标,并计算心肌梗死及缺血危险区面积。结果SP600125使I/R心肌损伤减轻,缩小梗死面积,在整个I/R期,SP600125组LVSP、±dp/dtmax和LVDP′的变化值均明显小于模型组(P<0.05或P<0.01)。结论SP6001253个剂量组均能改善大鼠心肌梗死面积及心脏I/R引起的心脏收缩功能。
Objective To investigate the effect and mechanism of JNK mitogen -activated protein kinases （JNK - MAPKs） inhibitor SP600125 on myocardial infarct size and heart function following ischemia and reperfusion （I/R） in anesthetized rats. Methods 30 healthy adult SD rats were randomly divided into six groups （ each n = 6） ： sham operation group （ SO）, ischemia reperfusion group （IR） and three JNK inhibitor groups. A silk suture was passed through the myocar- dium beneath a main branch of the left coronary artery I the SO group. For the experimental groups, the left coronary artery was occluded lasting for 30 minutes followed by reperfusion for 180 min. In the JNK inhibitor group, SP600125 was administered 5 minutes before the end of the ischemia period, followed by continuous intravenous infusion during reperfusion with a total dose of 4.7, 14.4 and 47.9 mg kg^-1 respectively. Controls rats received saline at a dose of 30 mg kg^-1. The changes of hemodynamics, such as LVSP, ＋ dp/dt max and LVDP＇ were determined during ischemic -reperfusion. Infarct size and risk area were measured after dyeing. Results The values of infarct size, LVSP, ±dp/dt max and LVDP＇ in the JNK inhibitor groups were significantly less than those in IR group（P 〈 0. 05 or P 〈 0.01 ）. Conclusion JNK inhibitor reduces infarct size and improves cardiac systole dysfunction induced by ischemic - reperfusion in anesthetized rats.
出处
《广东医学》
CAS
CSCD
北大核心
2009年第8期1052-1054,共3页
Guangdong Medical Journal
基金
广东省自然科学基金资助项目(编号:8151001002000018)
