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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。
Objective To study the protective effects of ulinastatin on the brain during epileptic seizures and its mechanism. Methods The epilepsy model was established in Wistar rats. After the model was successfully established and treated with 4 different treatments, group A received physiological saline injection, group B received carbamazepine, and group C received carbamazepine and a small amount of ulinastatin 10 000 U / kg). Group D received carbamazepine and massive ulinastatin (70 000 U / kg); S100β protein and nerve in each group at 24,48,72 and 96 h after the convulsions were achieved Enolase (NSE) water and tumor necrosis factor-α (TNF-α) and IL-1β levels were measured after 96 h. The number of caspase-3, bax and bcl-2 positive cells was detected by immunohistochemistry. The water maze was used to detect the cognitive function of rats. The effects of ulinastatin on epilepsy rats were compared between the model group and the blank control group and the model group. The blank control group was injected with the same amount of normal saline. Results The injection of ulinastatin reduced the levels of S100β and NSE, and the higher dose of ulinastatin was more effective (P <0.05). Ulinastatin inhibited the expression of TNF-α and IL-1β, (P <0.05). The positive cells of caspase-3 and bax were decreased and the positive cells of bcl-2 were increased after ulinastatin injection, and the effects of high-dose ulinastatin were more significant (P <0.05) ; Injection of ulinastatin can reduce neuronal apoptosis in hippocampal CA3 area, and high-dose ulinastatin effect was more significant (P <0.05); injection of ulinastatin can improve the cognitive function of epileptic rats, and high-dose Ulinastatin was more effective (P <0.05). Conclusion Ulinastatin may protect the brain of epileptic rats by inhibiting the expression of inflammatory cytokines and activating caspase-3 and bax, promoting bcl-2 protein activation and decreasing neuronal apoptosis.