p38MAPK在蛛网膜下腔出血后脑血管痉挛中的作用

Role of p38 mitogen-activated protein kinase on cerebral vasospasm after subarachnoid hemorrhage

目的探讨促分裂原活化蛋白激酶p38(p38MAPK)在蛛网膜下腔出血(SAH)后脑血管痉挛(CVS) 中的作用。方法采用枕大池二次注血的方法建立SAH模型。用酶联免疫吸附测定法(ELISA)、免疫组织化学、测量基底动脉横截面积的方法分别检测兔脑脊液肿瘤坏死因子-α(TNF—α)浓度变化及平滑肌细胞p38MAPK的表达与CVS程度变化的关系。结果 TNF—α浓度在注血后第3天达高峰,持续到第5天时,与注血前有明显差异(P< 0．01);平滑肌细胞p38MAPK表达增强;基底动脉横截面积则显著小于对照组(P<0．01)。应用p38MAPK特异性抑制剂SB203580干预后,TNF—α浓度显著降低到注血前水平,平滑肌细胞p38MAPK表达也明显减弱,基底动脉横截面积与对照组相比无明显差异(P>0．05)。结论 SAH后继发性的CVS可能是激活的p38MAPK通过对细胞因子增量调节机制作用的结果。

Objective To explore the role of p38MAPK in the development of cerebral vasospasm after subarachnoid hemorrhage（SAH）. Method Experemental SAH model in rabbits was made by injecting blood for two times,utilizing ELISA and immunohistochemical technique to measure cerebrospinal fluid concentrations of tumor necrosis factor-α and the expression levels of p38MAPK in smooth muscular cells related to the degree of cerebral vasospasm by measuring the cross-sectional area of each basilar arterial lumen. Results Cerebrospinal fluid con centrations of tumor necrosis factor-α on 3d reached the highest level after blood injection and had lasted till 5d, which was statistically significantly higher than before blood-injection （P〈0.01）. The expression of p38MAPK in smooth muscular cell significantly enhanced and the cross-sectional area of arterial lumen on 5d was statistically significantly smaller than the control group（P〈0.01）. Cerebrospinal fluid concentrations of tumor necrosis factor α showed significantly decreased changes and was no statistic significance after treatment with p38MAPK specific inhibitor SB203580（P〉0.05） ,moreover,p38MAPK was not detected in the vascular smooth muscle cell layer and the cross-sectional area of arterial lumen was no statistic significance compared to the the control group （P〉0.05）. Conclusion The upregulation of inflammatory cytokines,induced by the activation of p38MAPK,leads to the development of cerebral vasospasm（CVS） after SAH.