蛛网膜下腔出血后高迁移率族蛋白B1表达变化的调控机制研究

摘要

Objective To investigate regulation mechanism of the p38 mitogen activated protein kinase (p38MAPK) pathway in the expression of high mobility group box-1 protein (HMGB1) in basilar artery after subarachnoid hemorrhage. Methods Subarachnoid hemorrhage (SAH) was produced according to the double-hemorrhage method. p38MAPK inhibitor, SB203580, was injected into the cisterna magna just before production of the SAH. Enzyme-linked immunoadsordent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR), were used to examine the expression of HMGB1 after SAH. Results Vasospasm presented in the basilar artery gradually after SAH. The expression level of HMGB1 in basilar artery was increased at 1 d after treatment with SB, reached the peak at 5 ～7 d, and remained the relatively high level at 14 d. They were statistically significantly lower than those of the non-treated SAH group. Conclusion SB203580 can down-regulate the expression of HMGB1 in basilar artery after SAH. The p38MAPK signaling pathway may play an important role in the expression of HMGB1 after SAH.%目的 探讨蛛网膜下腔出血(SAH)后大鼠基底动脉中高迁移率族蛋白B1 (HMGB1)表达变化的p38丝裂原活化蛋白激酶(p38 MAPK)的调控机制.方法 通过枕大池二次注血方法制作大鼠SAH模型,注血前预先给予p38MAPK抑制剂SB203580,应用酶联免疫吸附试验(ELISA)、逆转录酶-多聚酶链反应(RT-PCR)分别从蛋白、基因水平分析抑制p38MAPK途径后发生SAH时基底动脉中HMGB1的表达情况.结果 SAH后大鼠基底动脉逐渐出现痉挛.抑制p38MAPK途径后基底动脉HMGB1蛋白、基因水平在SAH后升高,于5～7d达高峰,之后逐渐降低,14 d时仍维持较高水平.与枕大池二次注血组基底动脉HMGB1蛋白、基因水平相比,SB203580干预后基底动脉HMGB1浓度相比对照组每个时间点均降低.结论 SB203580能下调枕大池二次注血后基底动脉HMGB1蛋白和基因的表达,p38MAPK信号通路可能直接参与SAH后HMGB1的诱生机制.