异丙酚对心肌缺血再灌注大鼠的保护作用研究

Protective effect of propofol on myocardial ischemia-reperfusion injury in rats

目的：探究异丙酚对大鼠心肌缺血再灌注损伤的保护作用及其机制.方法：将60只健康雄性SD大鼠随机分为3组,每组20只,体重200～300 g.对照组（Ⅰ组）在冠状动脉左前降支近端穿线不缝扎;缺血再灌注组（Ⅱ组）用细线将冠状动脉左前降支穿线结扎30 min后,再灌注120 min;异丙酚组（Ⅲ组）在结扎冠脉左前降支10 min前,异丙酚5 mg/（kg·h）由股静脉持续静脉注射,至再灌注结束.3组恢复再灌注120 min后,取大鼠心肌组织通过透射电镜观察心肌细胞超微结构,比较3组细胞结构的改变,并检测心肌组织中TLR-4、TNF-α及NF-κb蛋白的表达水平.结果：Ⅰ组大鼠的心肌显微结构未见明显异常,而Ⅱ组和Ⅲ组大鼠的心肌细胞损伤明显,Ⅱ组损伤程度明显重于Ⅲ组.与Ⅰ组相比,Ⅱ组和Ⅲ组心肌TLR-4、TNF-α和NF-κb的表达水平明显上调（P＜0.05）;与Ⅱ组相比,Ⅲ组心肌TLR-4、TNF-α和NF-κb的表达水平明显下调（P＜0.05）.结论：静脉注射异丙酚对大鼠缺血心肌再灌注损伤有一定的保护作用,其保护机制可能与心肌细胞中TLR-4的活性受抑制,以及NF-κb和TNF-α等的表达水平下调有关.

Objective： To explore the protective effect of propofol on myocardial ischemia-reperfusion injury in rats. Method： Totally 60 healthy male SD rats were randomly divided into three groups （n=20 each） ,weighing 200 -200 g. Group I, sham operation; group II, myocardial isehemia-reperfusion injury was established by ligaturing the left anterior descending artery for 30 min, and then the time of reperfusion was 120 min; group III, myocardial ischemia-reperfusion injury was established as group II, and 10 rain before myocardial isehemia, propofol was given intravenously at 5 mg/ （k · h） until the 120 min reperfusion ended. Normal saline was given instead of propofol in groups I and II. After 120 min of reperfusion, the rats were killed to obtain myocardial tissues. The changes of myocardial cell ultrastructure were observed under transmission electron microscope, and the expression level of myocardial TLR- 4, TNF-α and NF-κB protein was determined. Result： There were no significant abnormity in myocardial microstructure of Group I. However, the myocardial cell injury was significant in Group II and III, and the damage degree of group II was significant serious than group IlL Compared with group I, the expressions of myocardial TLR - 4 mRNA, TNF-α and NF-κb protein were significantly increased in group II and III （P〈0.05） ; Compared with group II. the expressions of myocardial TI.R - ,1 mRNA. TNF-u and NF-αb protein were significantly lowered in group III （P〈0, 05）. Conclusion： Intravenous injection of protmfol can inhihil the activity of myocardial TI.R - 4 - and reduce the ex- pression of TNF-α and NF-κb protein.