乌司他丁对氯化锂-匹罗卡品诱发癫痫大鼠脑保护作用及其机制研究

目的 研究乌司他丁对癫痫发作时大脑的保护作用及其机制。方法 通过对Wistar大鼠建立癫痫模型,建模成功后并对其进行4种分组处理,即A组注射生理盐水; B组注射卡马西平; C组注射卡马西平和少量乌司他丁(10 000 U/kg); D组注射卡马西平和大量乌司他丁(70 000 U/kg); 测量每组达到惊厥标准后24、48、72、96 h不同时间段的S100β蛋白和神经烯醇化酶(NSE)水及96 h后肿瘤坏死因子-α(TNF-α)与IL-1β水平; 通过免疫组化检测caspase-3、bax与bcl-2阳性细胞数; 观察神经元凋亡情况; 用水迷宫检测大鼠的认知功能,通过模型组与空白对照组和模型组间对比分析乌司他丁对癫痫大鼠的影响; 空白对照组全程注射等量生理盐水。结果 注射乌司他丁能够降低S100β和NSE水平,并且大剂量乌司他丁效果更显著(P<0.05); 乌司他丁对TNF-α与IL-1β表达进行抑制,且大剂量乌司他丁效果更显著(P<0.05); 注射乌司他丁后caspase-3与bax的阳性细胞减少而bcl-2的阳性细胞增加,且大剂量乌司他丁效果更显著(P<0.05); 注射乌司他丁能够减少海马CA3区神经元凋亡,且大剂量乌司他丁效果更显著(P<0.05); 注射乌司他丁能够改善癫痫大鼠的认知功能,且大剂量乌司他丁效果更显著(P<0.05)。结论 乌司他丁可能是通过抑制炎症因子的表达和caspase-3与bax的激活,促进bcl-2蛋白激活,并减少神经元凋亡来对癫痫大鼠的大脑进行保护。

Protective effect and mechanism of ulinastatin on brain in rats with epilepsy induced by LICI-pilocarpin

ObjectiveTo study the protective effect and mechanism of ulinastatin on brain in rats during seizures.Methods Wistar rats were divided into 5 groups:control group with saline,A group with saline, B group with carbamazepine,C group with carbamazepine and little amount of ulinastatin(10 000 U/kg)and D group with carbamazepine and large amount of ulinastatin(70 000 U/kg).After seizures 24 h,48 h,72 h and 96 h,the level of S100β and NSE were detected.After 96 h,the level of TNF-α and IL-1β,the expression of caspase-3,bax and bcl-2,and the apoptosis of neuron in the CA3 area of hippocampus were detected.Water maze was used to assay cognitive function.Results The injection of ulinastatin reduced the contents of S100β,NSE,caspase-3,bax,the expression of TNF-α and IL-1β,and the apoptosis of neuron,increased the content of bcl-2,and ameliorated the cognitive function of rats with epilepsy.The effect was more significant when rats were treated with higher dose of ulinastatin(P<0.05).Conclusion The protective effect of ulinastatin on brain may be through inhibiting the expression of inflammatory cytokines,the activation of caspase-3 and bax,and the apoptosis of neuron,and improving the activation of bcl-2.