p38丝裂原活化蛋白激酶在实验性蛛网膜下腔出血后早期脑损伤中的作用

Role of p38 mitogen-activated protein kinase in early brain injury after experimental subarachnoid hemorrhage

摘要:

目的 探讨p38丝裂原活化蛋白激酶（p38MAPK）在蛛网膜下腔出血（SAH）后早期脑损伤（EBI）中的作用。方法 成年雄性SD大鼠随机分配至对照组、SAH组及p38MAPK干预组，每组18只。采用血管内穿刺法制作SAH模型，干预组于术前30 min经侧脑室注射p38MAPK特异性抑制剂SB203580，造模后24 h处死。观察各组大鼠脑含水量和神经功能评分，RT-PCR及免疫组化检测脑组织p38MAPK表达。结果 与对照组相比，SAH组大鼠脑含水量（t=-196.35，P<0.01）及p38MAPK的mRNA水平（t=-24.75，P<0.01）均明显升高，神经功能评分明显减低（t=201.08，P<0.01）。与SAH组相比，干预组脑含水量（t=75.67，P<0.01）及p38MAPK的mRNA水平（t=9.43，P<0.01）均明显下降，神经功能评分明显升高（t=-81.68，P<0.01）。免疫组化示SAH组及干预组均有p38MAPK表达，但干预组较SAH组表达水平明显下降（t=-3.37，P<0.01）。结论 p38MAPK在EBI形成机制中起重要作用，有望成为防治EBI的药物作用新靶点。

Abstract:

Objective To investigate the role of p38 mitogen-activated protein kinase (p38 MAPK) in early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH).Methods A total of 54 adult male Sprague-Dawley (SD) rats were equally and randomly divided into SAH group, control group, and p38 MAPK intervention group. An SAH model was established using intravascular silk puncture. The intervention group was given an intracerebroventricular injection of SB203580 (a specific inhibitor of p38 MAPK) at 30 minutes before modeling. All SD rats were sacrificed at 24 hours after modeling. The brain water content and neurological function score were determined. The expression of p38 MAPK in the brain was measured by RT-PCR and immunohistochemistry.Results The SAH group had significantly higher brain water content and mRNA level of p38 MAPK and a significantly lower neurological function score compared with the control group (t=-196.35, P<0.01; t=-24.75, P<0.01; t=201.08, P<0.01). The p38 MAPK intervention group had significantly lower brain water content and mRNA level of p38 MAPK and a significantly higher neurological function score compared with the SAH group (t=75.67, P<0.01; t=9.43, P<0.01; t=-81.68, P<0.01). The immunohistochemistry results showed that p38 MAPK protein was expressed only in the SAH group and the p38 MAPK intervention group, and the p38 MAPK group had significantly lower expression of p38 MAPK protein than the SAH group (t=-3.37, P<0.01).Conclusions p38 MAPK plays an important role in the formation of EBI, and it may be a new drug target for the prevention and treatment of EBI.