中文摘要：

目的探讨p38丝裂原活化蛋白激酶（p38 MAPK）在全脑缺血再灌注损伤大鼠海马神经元DNA修复中的作用。方法清洁级雄性SD大鼠108只，采用四血管阻断法建立大鼠全脑缺血再灌注模型，随机分为3组（n=36）：假手术组（S组）仅暴露双侧颈总动脉和椎动脉；缺血再灌注组（IR组）侧脑室注射1％DMSO溶液5μl，30min后行全脑缺血再灌注；p38MAPK抑制剂SB203580干预组（SB组）侧脑室注射SB203580溶液5μl（溶于1％DMSO溶液），30min后行全脑缺血再灌注。分别于再灌注2、6、12、24、48和72h时各组处死6只大鼠，提取海马组织观察神经元病理学结果，计算神经元凋亡指数（AI），测定磷酸化的p38MAPK蛋白及Ku70蛋白表达水平。结果与S组比较，IR组和SB组各时点AI升高，p-p38 MAPK蛋白表达上调，p-Ku70蛋白表达下调（P〈0．05或0．01），病理损伤明显；与IR组比较，SB组各时点AI降低，p-p38MAPK蛋白表达下调，p-Ku70蛋白表达上调（P〈0．01），病理损伤程度减轻。结论p38MAPK可能通过下调DNA修复酶KuT0蛋白的表达，使海马神经元DNA修复功能受损，导致神经元凋亡，参与全脑缺血再灌注损伤。

英文摘要：

Objective To investigate the role of p38 mitogen-activated protein kinase （MAPK） in the DNA repair in hippocampus in a rat model of global cerebral ischemia-reperfusion （I/R）. Methods One hundred and eight male 55-65 day old SD rats weighing 280-320 g were divided into 3 groups （ n = 36 each） ： group Ⅰ sham operation （S）, group Ⅱ I/R and group Ⅲ SB203580 ＋ I/R （SB）. The animals were anesthetized with intraperitoneal 1% pentobarbitad 40 mg/kg, Global cerebral ischemia-reperfusion was produced by 4 vessel method. Bilateral vertebral arteries were electrically cauterized and bilateral common carotid arteries were clamped for 5 min with atraumatic mini-clamp. In group Ⅲ 5 μl 0.1 nmol/μl p38 MAPK inhibitor, SB203580 （in 1% DMSO） was injected into the lateral ventricle of the brain 30 min before cerebral global I/R. Six animals were killed at 2, 6, 12, 24, 48 and 72 h of reperfusion respectively. The hippocampus was isolated for microscopic examination. Apoptosis index was calculated and p-p38 MAPK and DNA repair protein Ku70 protein expression was determined. Results AI was significantly higher, p-p38 MAPK protein expression was up-regulated and p-Ku70 protein expression was down-regulated and there was severe histological damage in I/R and SB groups as compared with group S. Pretreatment with SB203580 attenuated the above-mentioned I/R induced cerebral changes. Conclusion p38 MAPK damages DNA repair function by down-regulating Ku70 protein expression during global cerebral I/R and induces neuronal apoptosis.