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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24h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差异(P>0.05)。再灌注后24h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24h细胞形态较好,坏死程度较轻。免疫组化检测结果:空白对照组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24h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24hBax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再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。
Objective: To investigate the effect of SB202190 on focal cerebral ischemia-reperfusion injury in rats and to explore the role and possible mechanism of SB202190 in cerebral ischemia protection. Methods: The rat middle cerebral artery occlusion (MCAO) model of ischemia-reperfusion injury was established by thread occlusion. Male SD rats were randomly divided into 5 groups: blank control group, sham operation group, ischemia reperfusion group, administration group and vehicle group. Six rats in each group were injected intracerebroventricularly with p20MAPK SB202190 and 1% DMSO respectively. The neurobehavioral scores of rats were respectively evaluated by Nissl staining. The morphological changes of cells in ischemic zone were observed by Nissl staining. The changes of Bcl-2 and Bax positive neurons were detected by immunohistochemistry. Results: The score of neurological function of rats at 24h after ischemia-reperfusion was significantly lower than that of sham-operation group (P <0.05). The score of neurological function of the rats in treatment group was significantly higher than that of ischemia-reperfusion group Difference (P <0.05). However, there was no significant difference in the neurological function score between the vehicle group and the ischemia-reperfusion group (P> 0.05). Microscopically, after 24 hours of reperfusion, most of the cells showed atrophy, decreased cytoplasm, increased nuclear staining and increased cell gap. Compared with the ischemia-reperfusion group, the morphology of the cells in the drug-treated group was better and the degree of necrosis was lighter 24 h after reperfusion. Immunohistochemical results showed that a very small number of Bcl-2 and Bax-positive cells were scattered in the blank control group and the sham operation group, with no significant difference between the two groups (P> 0.05). A large number of Bax positive cells were observed 24 h after reperfusion, Compared with the sham group, there was a significant difference (P <0.05), while the Bcl-2 positive cells had no significant change (P> 0.05). Compared with the ischemia reperfusion group, the 24hBax positive cells in the reperfusion group were significantly decreased (P <0.05). The number of Bcl-2 positive cells was significantly increased compared with ischemia reperfusion group (P <0.05). CONCLUSIONS: SB202190, a specific inhibitor of p38MAPK, can improve neurological deficits and neuronal morphological changes after focal cerebral ischemia / reperfusion in rats. SB202190 can change the expression of Bcl-2 and Bax expression, which may be SB202190 anti-apoptosis mechanism.