热休克预处理对大鼠缺血再灌注心肌保护作用机制的探讨

Protective effect of heat-shock pretreatment on rat ischemia-reperfusion myocardium

目的:观察心肌缺血再灌注时P-选择素(Ps)表达情况;探讨热休克蛋白(HSP)对缺血再灌注心肌Ps及细胞凋亡表达的影响。方法:成年雌性W istar(n=40)大鼠随机分为3组。热休克组全麻后高热处理造成热休克动物模型,对照组及假手术组仅予全麻处理。24 h后热休克组及对照组结扎左冠状动脉前降支(LAD)1 h,再灌注2 h造成心肌缺血再灌注动物模型。假手术组只于LAD处穿线而不结扎。术毕测心梗范围、HSP70、Bax、Bc l-2、Ps、凋亡细胞及血清CK-MB。结果:热休克组HSP70表达高于对照组及假手术组(P<0.05),后两组无明显差别(P>0.05);热休克组心梗范围小于对照组(P<0.05),CK-MB值低于对照组(P<0.01),凋亡细胞、Bax及Ps表达低于对照组(P<0.05),两组Bc l-2表达无显著差别(P>0.05);假手术组无Ps表达。结论:HSP70可抑制缺血再灌注诱导的心肌细胞凋亡,抑制Bax表达致Bax/Bc l-2比值下降为其机制之一;Ps参与心肌缺血再灌注损伤;HSP70可能有抑制心肌Ps表达的作用,这或许是热休克预处理对大鼠缺血再灌注心肌的另一保护机制。

AIM ： To investigate the changes of expression of P - selectin （Ps） in ischemia - reperfusion myocardium and to observe the effects of heat shock protein （HSP） on the expression of Ps and apoptosis. METHODS： Mature female Wistar rats （ n = 40） were divided into three groups at random. Under general anesthesia, the rats in heat - shock group were subjected to whole - body hyperthermia, and those in the other two groups were treated with anesthetic alone. Twenty - four hours later, the animals in heat - shock group and in control group were subjected to surgical operative ligation of coronary left anterior descending branch （ LAD ） for 1 h, then accepted reperfusion for 2 h. Those in sham operation group were also performed surgical operation without LAD ligation for 3 h. After operation, the CK - MB in blood serum, infarct size of left ventricles, HSP70, Bax, Bcl - 2, Ps and apoptosis cells were measured. RESULTS ： The amount of HSP70 in heat - shock group was significant higher than that in control group and in sham operation group （ P 〈 0. 05 ）. There was no difference between control group and sham operation group （P 〉0. 05 ）. Compared with control group, the infarct size, CK -MB, apoptosis cells, Bax and Ps in heat -shock group were significantly reduced （P 〈 0. 05 ）. However, expression of Bcl - 2 was similar （ P 〉 0. 05 ）. No expression of Ps in sham operation group was detected. CONCLUSIONS ： HSP70 may reduce myocardial apoptosis during ischemia - reperfusion. One of the mechanisms is that HSP70 restraines the expression of Bax and Bax/Bcl-2. Ps plays an injurious role in ischemia- reperfusion myocardium. HSP70 is likely to restrain Ps from expression, which may be one of the mechanisms by which heat - shock pretreatment plays a protective role in ischemia - reperfusion myocardium.