p38丝裂原活化蛋白激酶信号通路特异性阻滞药对癫痫模型大鼠神经细胞的保护作用研究

Protective Effects of p38MAPK Inhibitor on Nerve Cells in Epilepsy Model Rats

目的:研究p38丝裂原活化蛋白激酶信号通路特异性阻滞药SB203580对癫痫模型大鼠神经细胞的保护作用。方法:取大鼠随机分为正常对照组、模型组和SB203580低、中、高剂量(5、10、20mg.kg-1)组,每组10只,后4组腹腔注射戊四唑建立癫痫模型,SB203580各剂量组建模前10min腹腔注射相应药物。建模给药后按Racine分级标准对各组大鼠进行行为学评价,建模给药后2h检测各组脑组织中乳酸脱氢酶(LDH)释放率,采用免疫组化法和免疫印迹法检测海马组织中半胱氨酸天冬氨酸蛋白酶3(Caspase-3)的表达。结果:正常对照组无癫痫发作;与正常对照组比较,模型组癫痫发作程度明显增强,LDH释放率明显升高,Caspase-3阳性细胞数及其表达明显增加(P<0.01);与模型组比较,SB203580各剂量组癫痫发作程度明显减轻,LDH释放率明显降低,Caspase-3阳性细胞数及其表达明显减少(P<0.05或P<0.01),且与剂量成正相关。结论:SB203580可能通过间接抑制Cas-pase-3表达实现对癫痫模型大鼠神经细胞的保护作用。

OBJECTIVE： To study the protective effect of p38MAPK inhibitor SB203580 on nerve cell of epilepsy model rats. METHODS： Rats were randomly divided into normal control group, model group and SB203580 low-dose, medium-dose and high-dose groups （5, 10, 20 mg.kg-1） with 10 rats in each group. The latter 4 groups were given intraperitoneal injection of penta- methylenetetrazol to establish epilepsy model, SB203580 groups received intraperitoneal injection of relevant drugs 10 min before modeling, and the behavior of rats was observed using Racine scale standard after modeling and medication. The release rate of LDH in cerebral tissue was determined 2 h after modeling and medication. The expression of Caspase-3 in the hippoacampus of rats was examined by immunohistochemistry and western blotting. RESULTS： Normal control group had no epileptic seizure. Compared with normal control group, the degree of epileptic seizure was enhanced significantly, the content of LDH in cerebral tissue was in- creased significantly, the number and expression of Caspase-3 positive cells were enhanced significantly in model group （P〈0.01）. Compared with model group, the degree of epileptic seizure was alleviated, the content of LDH in cerebral tissue was decreased significantly, the number and expression of Caspase-3 positive cells were also decreased significantly in SB203580 groups （P〈 0.05 or P〈0.01）, which were positively correlated with drug dosage. CONCLUSION： SB203580 has protective effect on nerve cell of epilepsy model rats by inhibitin~ the expression of Caspase-3 indirectly.