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目的观察托吡酯对癫小鼠治疗过程中产生认知功能障碍可能机制的探讨。方法选90只清洁级KM小鼠,随机取出10只作为正常对照组,其他小鼠制备癫模型。成模小鼠随机分成癫模型组、托吡酯低剂量治疗组、托吡酯中剂量治疗组、托吡酯高剂量治疗组、左乙拉西坦治疗组,每组10只。给药干预14d后,小鼠进行Morris水迷宫试验检测行为学改变后处死小鼠取脑组织进行免疫组化和Western blot方法检测,检测小鼠海马组织5-HT、Bcl-2蛋白及iNOS蛋白表达。所得数据进行统计分析,各组间均数比较进行方差分析和t检验,P<0.05为有统计学意义。结果水迷宫结果显示,癫模型组逃避潜伏期要长于同日正常对照组,差异有统计学意义(P<0.05),左乙拉西坦治疗组逃避潜伏期要低于癫模型组,差异有统计学意义(P<0.05),托吡酯高剂量治疗组的逃避潜伏期要长于癫模型组,差异有统计学意义(P<0.05)。iNOS、5-HT和Bcl-2结果显示,与正常对照组比较,癫模型组iNOS含量增加,5-HT和Bcl-2含量减少,差异有统计学意义(P<0.05)。与癫模型组比较,左乙拉西坦治疗组iNOS含量减少,5-HT和Bcl-2含量升高,差异有统计学意义(P<0.05)。与癫模型组比较,托吡酯高剂量治疗组的iNOS含量稍高,5-HT和Bcl-2含量稍有减少,差异无统计学意义。结论较高剂量托吡酯能够使癫小鼠海马组织5-HT和Bcl-2含量大大减少从而降低对海马神经细胞的抗凋亡作用,间接促进小鼠海马区神经细胞凋亡,从而导致小鼠认知功能障碍。
Objective To investigate the possible mechanism of topiramate on cognitive dysfunction induced by epilepsy in mice. Methods Ninety clean KM mice were randomly divided into normal control group and other mice. Mice were randomly divided into epilepsy model group, topiramate low-dose treatment group, topiramate middle-dose treatment group, topiramate high-dose treatment group, levetiracetam treatment group, 10 rats in each group. After intervention for 14 days, the mice were subjected to Morris water maze test to detect the behavioral changes, then the mice were sacrificed and the brain tissues were harvested for immunohistochemistry and Western blot. The 5-HT, Bcl-2 protein and iNOS protein expression. The data were statistically analyzed, the mean between the groups were analyzed by ANOVA and t test, P <0.05 was considered statistically significant. Results The water maze results showed that the escape latency of the epilepsy model group was longer than that of the normal control group on the same day (P <0.05), and the escape latency of the levetiracetam treatment group was lower than that of the epilepsy model group (P <0.05). The escape latency of high-dose topiramate treatment group was longer than that of epilepsy model group, the difference was statistically significant (P <0.05). The results of iNOS, 5-HT and Bcl-2 showed that iNOS content and 5-HT and Bcl-2 levels in epilepsy model group were significantly decreased compared with those in normal control group (P <0.05). Compared with the model group, the iNOS content and the content of 5-HT and Bcl-2 in levetiracetam group were significantly decreased (P <0.05). Compared with the epilepsy model group, high-dose of topiramate treatment group slightly higher iNOS content, 5-HT and Bcl-2 content decreased slightly, the difference was not statistically significant. Conclusion Higher doses of topiramate can significantly reduce the 5-HT and Bcl-2 levels in the hippocampus of epileptic mice, thereby reducing the anti-apoptotic effect on hippocampal neurons and indirectly promoting neuronal apoptosis in the hippocampus of mice. cognitive dysfunction.