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目的探讨妥泰在治疗癫小鼠过程中对小鼠认知能力的影响。方法选80只清洁级昆明(KM)小鼠随机取出10只作为正常对照组,其余70只小鼠应用戊四氮(PTZ)制备癫点燃模型,每日上午9:00~10:00,按35mg/kg剂量腹腔注射,连续14d,正常对照组给予等容生理盐水。14d后,通过Racine分级标准筛选连续3d达到Ⅳ级以上KM小鼠进行第二阶段药物干预,将成模小鼠随机分成癫模型组、妥泰低剂量治疗组、妥泰中剂量治疗组、妥泰高剂量治疗组、左乙拉西坦治疗组,每组10只。各药物治疗组和模型组继续每日上午9:00~10:00PTZ腹腔注射。在PTZ腹腔注射前,妥泰低剂量治疗组灌胃给予小鼠妥泰70mg/kg剂量,妥泰中剂量治疗组按140mg/kg灌胃,妥泰高剂量治疗组按280mg/kg灌胃,正常对照组和癫模型组灌胃等容蒸馏水。给药干预14d后,小鼠进行Morris水迷宫试验检测认知能力,之后断头处死小鼠,进行脑组织SOD含量和MDA含量、iNOS蛋白表达,病理HE染色观察小鼠脑部海马结构变化。结果与正常对照组比较,癫模型组小鼠平均逃避潜伏期时间明显升高,SOD含量明显降低,MDA和iNOs含量明显升高,海马HE图片显示海马组织结构松散,出现大量损伤神经元细胞。妥泰高剂量治疗组平均逃避潜伏期时间明显高于其他各组,SOD含量明显降低,MDA和iNOs含量明显增高,差异有统计学意义(P<0.05)。HE病理结果显示妥泰高剂量治疗组海马组织排列松散,并出现较多肿胀和破损异常的细胞。结论较大剂量妥泰能够对PTZ所致癫小鼠造成氧化损伤,导致癫小鼠认知功能障碍。
Objective To investigate the effect of topiramate on cognitive ability of mice in the treatment of epileptic mice. Methods Totally 80 clean-grade Kunming (KM) mice were randomly divided into normal control group (n = 10) and the other 70 mice were treated with pentylenetetrazole (PTZ) to prepare epileptic model. The rats were exposed daily from 9:00 to 10:00, By 35mg / kg dose intraperitoneal injection, continuous 14d, normal control group given equal volume of saline. After 14 days, the second-stage drug intervention was performed on the third-generation KM mice which reached the third grade or higher by Racine grading standard for three consecutive days. The model mice were randomly divided into epilepsy model group, low-dose and high-dose group, Thai high-dose treatment group, levetiracetam treatment group, 10 rats in each group. Each drug treatment group and model group continue daily 9: 00 ~ 10: 00 PTZ intraperitoneal injection. In the PTZ intraperitoneal injection, low-dose high-dose treatment group was given intragastric administration of the dose of topiramate 70mg / kg, topiramate dose group treated with 140mg / kg gavage, high-dose of topiramate treatment group by 280mg / kg gavage, Normal control group and epilepsy model group intragastric distilled water. The mice were subjected to Morris water maze test 14 days after intervention to detect cognitive ability. After that, the mice were sacrificed and their SOD and MDA contents, iNOS protein expression and histopathological HE staining were observed. Results Compared with the normal control group, the mean escape latency time, the content of SOD and the content of MDA and iNOS in the epilepsy model group were significantly increased. The hippocampus HE pictures showed that the hippocampus tissue was loose and a large number of injured neurons appeared. The average escape latency of high-dose treatment group was significantly higher than that of other groups, the content of SOD was significantly decreased and the content of MDA and iNOS were significantly increased (P <0.05). HE pathological results showed that hippocampal high-dose treatment group, loosely arranged hippocampal tissue, and more cells with abnormal swelling and damage. Conclusion Higher doses of topiramate can cause oxidative damage to epileptic mice induced by PTZ, resulting in cognitive dysfunction in epileptic mice.