p38丝裂原活化蛋白激酶抑制剂对急性重症胰腺炎大鼠神经元的保护作用

Effect of p38 mitogen-activated protein kinase inhibitor on nerve protection of rats with severeacute pancreatitis

目的研究p38丝裂原活化蛋白激酶抑制剂SB203580对急性重症胰腺炎(SAP)大鼠神经元的保护作用。方法 45只健康雄性大鼠随机分为对照组、模型组和抑制剂组,每组15只。模型组大鼠给予质量分数5%牛磺胆酸钠2 mg·kg^(-1),经胰胆管注入胰腺腺体内;抑制剂组大鼠在建模后立即给予腹腔注射SB203580 10 mg·kg^(-1),对照组大鼠开腹后给予等量生理盐水经胰胆管注入胰腺腺体内。术后24 h采用免疫组织化学染色和免疫印迹法观察大鼠大脑皮层神经元中磷酸化p38(p-p38)和caspase-3的表达。结果模型组大鼠大脑皮层区p-p38、caspase-3阳性神经元数(21.6±2.5、33.1±3.8)较对照组(1.1±0.6、2.0±0.5)显著增加(P<0.05);抑制剂组大鼠大脑皮层区pp38、caspase-3阳性神经元数(15.3±1.3、16.6±1.4)较模型组显著减少(P<0.05)。结论 p38丝裂原活化蛋白激酶抑制剂SB203580通过抑制p38信号通路下调caspase-3表达,从而对SAP大鼠神经元起到保护作用。

Objective To investigate the effect of p38 mitogen-activated protein kinase inhibitor SB203580 on nerve protection of rats with severe acute pancreatitis（SAP）. Methods Forty-five healthy male rats were randomly divided into control group, model group and inhibitor group ,with 15 cases in each group. The model group was induced by retrograde bile-pancreatic duct infusion of 5% sodium taurocholate（2 mg·kg^-1）. The inhibitor group was induced by intraperitoneal injection SB203580 （ 10 mg · kg^-1 ） after modeling. The control group was infused 0.9% sodium chloride by retrograde bile-pancreatic duct. Caspase- 3 and phosphorylation of p38 （p-p38） were detected to observe the changes of positive cell numbers and the expression level in the cerebral cortical of the rats by immunohistochemistry and Western blot. Results The positive cell number of p-p38 and caspase-3 （21.6 ± 2.5,33.1 ± 3.8） in the the cerebral cortex increased significantly in the rats of model group compared with those in control group（ 1.1 ±0.6,2.0 ±0. 5） （P 〈0.05） ,which were reduced significantly in the rats of inhibitor group （15.3 ±1.3,16. 6 ± 1.4） compared with those in model group （ P 〈 0. 05 ）. Conclusion p38 mitogen-activated protein kinase inhibitor SB203580 may play a neural protection effect through inhibition of p38 signaling pathway to inhibiting caspase-3 expression down.