p38MAPK抑制剂对兔脑血管痉挛病理变化的影响

Effect of the JNK inhibitor on the development of cerebral vasospasm after subarachnoid hemorrhage in rabbits

目的观察兔脑血管痉挛(CVS)后基底动脉病理学改变、p38MAPK的表达及其抑制剂SB203580对脑血管痉挛的影响,以探讨蛛网膜下腔出血(SAH)后CVS细胞信号通路转导机制。方法①采用二次枕大池注血建立兔CVS模型。②采用免疫组织化学技术动态观察兔基底动脉血管壁组织病理改变,观察使用SB203580干预后对病理学改变的影响。结果①SAH组基底动脉管腔狭窄,以SAH后7d时为最重;SAH+SB203580组和对照组无明显差异,其与同时段的SAH组比较血管变化明显减轻。②应用p38MAPK特异性抑制剂的SB203580组兔脑基底动脉狭窄改善,TUNEL染色阳性内皮细胞与SAH组相比下降,有显著差异,同时病理检查显示基底动脉管壁增厚、内皮细胞凋亡样改变减轻,对照组与SB203580组比较差异不明显。结论①p38MAPK信号转导通路引起血管内皮细胞的凋亡,是参与形成CVS机制之一。②p38MAPK抑制剂SB203580可以缓解血管内皮细胞的凋亡,有效缓解CVS。

Objective To observe the pathological changes in the basilar arteries after cerebral vasospasm （CVS） and the effect of its inhibitor,SB203580 on CVS and p38MAPK expression in rabbits in order to explore signal pathway mechanism in CVS after subarachnoid hemorrhage （SAH）.Methods The model of CVS after SAH was established in the rabbits.The pathological changes and the expression of p38MAPK in the basilar arteries of the rabbits were determined respectively by immunohistochemical techniques.The effects of SB203580 on CVS and pathological changes were observed.Results The lumens of the basilar arteries became narrow and their vascular walls were infiltrated into by apoptosis cells in SAH group,where the most significant changes in the basilar arteries were found 7 days after SAH.The change in the basilar arteries of SAH＋SB203580 group was significantly alleviated compared to that of SAH group.Basilar arteries in SAH group and DMSO group were narrower compared with control group.The upregulation of P38MAPK was detected and lots of positive cells which was in brown on the vascular wall.Apoptotic-like changes such as condensation of cytoplasm,positive staining of TUNEL protein were observed in VECs in SAH group compared with Control group.The SAH group had differences when it compared with control group.There was no difference between the SAH group and DMSO group.In the treatment group,SP600125 significantly ameliorated the pathological changes including thickness of arterial wall,degeneration and necrosis of endothelial cells （P0.05） when compared with SAH group.Conclusion p38MAPK signal pathway regulates immune is one of mechanism producing CVS.P38MAPK inhibitor,SB203580 may regulate apoptosis of vessel walls and effectively alleviate CVS after SAH in the rabbits.