P38MAPK调控重症急性胰腺炎大鼠海马神经元COX-2和PGE2表达的研究

Expression of P38MAPK regulates COX-2 and PGE2 of hippocampal neurons in rat model of severe acute pancreatitis

目的：研究P38丝裂原活化蛋白激酶（P38MAPK）对重症急性胰腺炎（SAP）大鼠海马神经元环氧合酶-2（COX-2）和前列腺素E2（PGE2）表达的调控作用。方法：雄性健康SD大鼠36只,体重220~260 g,随机分为3组。SAP模型组：采用向胰胆管内注入5%牛磺胆酸钠（2 mg/kg）的方法制备SAP动物模型;抑制剂组：SAP建模成功5 min后,大鼠尾静脉注射P38MAPK抑制剂SB203580（10 mg/kg）;对照组：行剖腹术翻动胰腺和十二指肠后缝合腹腔。各组大鼠分别于术后24 h,用Nissl染色和免疫组化法观察脑组织病理改变的情况,用Western Blot检测脑组织中p-P38蛋白、COX-2和PGE2的表达情况。结果：模型组大鼠海马CA1区局部锥体细胞缺失,p-P38、COX-2和PGE2阳性细胞数明显增加（P〈0.01）,且相应蛋白表达显著升高（P〈0.01）;SB203580处理组以上变化明显减轻或不明显（P〈0.01）。结论：P38MAPK对实验SAP大鼠海马COX-2和PGE2表达具有显著调控作用,而P38MAPK抑制剂SB203580则对SAP大鼠海马神经元具有一定保护作用。

Objective： To investigate the effect of P38 mitogen-aetivated protein kinase（P38MAPK） in regulating the expression of cyelooxygenase-2 （ COX-2 ） and prostaglandin E2 （ PGE2 ） in hippocampal neurons in a ratmodel ratof severe acute pancreatitis （SAP）. Methods：Thirty-six healthy male SD rats （weighing 220-260 g） were randomly divided into 3 groups： （1） SAP model group, treated with 5% sodium taurocholate（2 mg,/kg）, （2）inhibitor group, treated with SB203580 （10 mg/kg） 5 min after injection of 5% sodium taurocholate, （3）control group was only sutured in abdominal wall after laparotomy flip pancreatic. 24 h after surgery, the pathological changes of brain tissue in each group were ob- served by Nissl staining and Immunohistochemistry, respectively. The expression of p-P38, COX-2 and PGE2 were detec- ted in rat hippocampal by Western Blot. Resnlts：In the model group, the somepyramidal cells disappeared in the CAI re- gion of the hippoeampus, and the number of p-P38, COX-2 orPGE2 positive cells were significantly increased （P 〈 0.01 ） , and the protein expression was significantly increased（ P 〈 0.01 ）, and these changes were significantly reduced or not significant after SB203580 treatment（ P 〈 0. 01 ）. Conclusion ：The results showed that P38MAPK had a significant effect on the expression of COX-2 and PGE2 in the hippocampus of SAP rats, and P38MAPK inhibitor SB203580 had a protective effect on hippocampal neurons of SAP rats.