p38 MAPK在大鼠局灶性脑缺血再灌注损伤中的作用

The role of p38 MAPK in focal cerebral ischemia/reperfusion injury in rats

目的探讨p38 MAPK在大鼠脑缺血再灌注损伤中的作用及可能机制。方法雄性SD大鼠随机分为5组:空白对照组、假手术组、缺血再灌注组、给药组及溶媒组。除对照组及假手术组外各组采用线栓法建立大鼠大脑中动脉缺血再灌注损伤模型。给药组和溶媒组分别侧脑室注射p38 MAPK特异性抑制剂SB202190及1%DMSO。每组分别进行行为学评分和检测Bcl-2、Bax表达的变化。结果①行为学结果:空白对照组及假手术组,缺血再灌注后24 h大鼠神经功能评分降低,给药组大鼠神经功能评分高于缺血再灌注组,有统计学差异(P<0.01)。②免疫印迹检测结果:空白对照组及假手术组可见少量Bcl-2、Bax蛋白表达,两组间无统计学差异(P>0.05);缺血再灌注组再灌注后24 h可见Bcl-2表达减少,但与空白对照组及假手术组相比无统计学差异(P>0.05),而再灌注后24 h可见Bax蛋白表达明显增加,与空白对照组及假手术组相比有统计学差异(P<0.05);给药组与缺血再灌注组相比再灌注后24 h可见Bax蛋白表达明显减少(P<0.05),而Bcl-2蛋白表达明显增加(P<0.05)。结论抑制p38 MAPK激活可以减轻大鼠脑缺血再灌注时的脑神经元的凋亡。

Objective To study the mechanism of p38 MAPK after focal cerebral ischemia/reperfusion injury in rats.Methods Healthy male Sprague-Dawley rats were randomly divided into five groups： normal control group,sham group,ischemia/reperfusion group,SB202190 group and DMSO group.Except normal control group and sham group,rats′ cerebral ischemia/reperfusion model was established with suture method.In SB202190 group and DMSO group,SB202190（the specific inhibitor of p38 MAPK） and 1% of dimetyl sulphoxide（DMSO） were injected into the lateral ventricle respectively.The expression of Bcl-2 and Bax protein was studied and the behavioral score was recorded.Results ① Behavioral results： rats′ nerve function score of control group and sham group decreased after ischemia-reperfusion 24 h.Neurological function in SB202190 group was higher than in IR group,and there was statistical significance（P0.01）.② Western blot test results： both Bcl-2 and Bax protein all express a few in normal control group and sham group,but there was no difference（P0.05）.The expression of Bcl-2 protein decreased in IR group but there was no obvious statistical difference,Bax protein increased obviously at 24 h after ischemia/reperfusion（P0.05）.Compared with IR group,the expression of bax protein in SB202190 group decreased,and there was obvious increases of Bcl-2 protein in SB202190 group（P0.05）.Conclusion Inhibition of the p38 MAPK can protect neural function from being injured after focal cerebral ischemia/reperfusion injury in rats.