大鼠局灶性脑缺血再灌注损伤时SB202190的保护作用

目的:研究SB202190对大鼠局灶性脑缺血再灌注损伤的影响,探讨SB202190在脑缺血保护中的作用及可能机制.方法:采用线栓法建立大鼠大脑中动脉缺血再灌注损伤模型.雄性SD大鼠.随机分成5组:空白对照组、假手术组、缺血再灌注组、给药组及溶媒组.每组6只大鼠,给药组及溶媒组分别侧脑室注射p38MAPK特异性抑制剂SB202190及1%DMSO.各组分别进行大鼠神经功能的行为学评分:Nissl染色观察缺血区细胞形态变化;免疫组化检测Bcl-2、Bax阳性神经元变化.结果:缺血再灌注后24 h大鼠神经功能评分显著低于假手术组,有统计学差异(P<0.05),给药组大鼠神经功能评分显著高于缺血再灌注组,有统计学差异(P<0.05).而溶媒组神经功能评分与缺血再灌注组相比无统计学关差异(P>0.05).再灌注后24 h镜下可见大部分细胞萎缩,胞浆减少,胞核浓染,细胞间隙增大.给药组与缺血再灌注组相比再灌注后24 h细胞形态较好,坏死程度较轻.免疫组化检测结果:空白对照绀及假手术组可见极少数Bcl-2、Bax阳性细胞散在分布,两组间无统计学差异(P>0.05);再灌注后24 h可见大量Bax阳性细胞,与假手术组相比有统计学差异(P<0.05),而Bcl-2阳性细胞无明显变化(P>0.05);与缺血再灌注组比较给药组再灌注后24 h Bax阳性细胞明显减少.有统计学差异(P<0.05),Bcl-2阳性细胞与缺血再灌注组比较明显增多,有统计学差异(P<0.05).结论:p38MAPK特异性抑制剂SB202190可以改善大鼠局灶性脑缺血冉灌注后产生的神经功能缺损症状及神经细胞形态学改变:SB202190能改变局灶性脑缺血再灌注后Bcl-2及Bax的表达,这可能是SB202190抗细胞凋亡的机制之一.

The protective effect of the inhibitor of p38MAPK's SB202190 on focal cerebral ischemia/ reperfusion in rats

Objective:To study the effect of the inhibitor of p38MAPK(SB202190)on focal cerebral ischemia/reperfusion in rats,and furth explore the nourprotective effect and mechanism of SB202190 on focal cerebral ischemia/reperfusion. Methods: The acute focal cerebral ischemia/reperfusion models were established by suture emboli. Healthy male Sprague-Dawley rats were randomly divided into five groups:normal control group,sham group,ischemia/reperfusion group,SB202190 and DMSO group. In SB202190 and DMSO group,SB202190(the specific inhibitor of p38MAPK) and 1 % dimetyl sulphoxide(DMSO) were injected into the lateral ventricle respectively. Behavior scores of rat neuralogical fanction were penformed for each group The rats were sacrificed at 24 h after ischemia/reperfusion. Nissl staining is rsed to observe morphologic changes of neuron cells in ischemia/reperfusion injury region;and immunohisochemistry is used to detect Bcl-2 and Bax protein positive cell. Results: Rats of ischemia/reperfusion group had a lower score of neurological function compared with sham group(P < 0.05). The score in SB202190 group was significantly higher than that in ischemia/reperfusion group(P < 0.05),but there was no difference between ischemia/reperfusion group and DMSO group(P > 0.05).There were massive cellular necrosis found in rats at 24 h after ischemia/reperfusion,the form of neuron cell were atrophica,cellular plasm dried up and nucleus were densely stained,intercellular space were more lager than normal neuron cell. SB202190 group:Compared with the ischemia/reperfusion group,the cellular swelling was more light at 24 h after ischemia/reperfusion,and the injury of cellular necrosis was mild after ischemia/reperfusion;Immunohisochemistry staining to detect Bcl-2 and Bax positive neurons:There were a few Bcl-2 and Bax positive cells,which distributed dispersively in ischemia/reperfusion injury region,and there was no obvious difference between normal control group and sham group(P > 0.05);For the Ischemia/reperfusion group:There were massive Bax positive cells distributed in ischemia/reperfusion injury region at 24 h after ischemia/reperfusion,but Bcl-2 positive cells were no obvious change(P > 0.05);For the SB202190 group:Bcl-2 positive cells obvious increased at 24 h after ischemia/reperfusion(P > 0.05),but Bax positive cells obvious decreased compared with the Ischemia/reperfusion group. Conclusion:The inhibitor of p38MAPK(SB202190) can protect neural function from ischemia/reperfusion injury after ischemia/reperfusion in rat. SB202190 can reduce the region of ischemia/reperfusion injury,and regulate the activation of Bcl-2 and Bax protein after ischemia/reperfusion in rat,and it may be one of the possible mechanisms of antiapoptotic effect of SB202190.