丙戊酸钠对匹罗卡品致痫大鼠GABAB受体表达及认知功能的影响

Effects of sodium valproate on GABAB receptor in hippocampus of pilocarpine induced kindled rats model and effects on cognitive function

目的研究丙戊酸钠对匹罗卡品致痫大鼠GABAB受体(GABABR)表达及认知功能的影响。方法建立氯化锂-匹罗卡品致痫模型,随机分成正常对照组、丙戊酸钠组、生理盐水组及单纯点燃组。通过避暗实验、水迷宫观察大鼠认知情况,免疫组化、荧光定量PCR、免疫印迹检测大鼠海马组织内GABABR蛋白相对表达情况。结果避暗实验4组大鼠穿梭次数分别为6.8±0.6、5.2±0.3、3.4±0.3、3.6±0.3,潜伏期分别为26.1±3.4、62.2±6.9、92.8±8.3、91.2±9.1,与水迷宫实验行为学变化趋势一致,显示致痫大鼠较正常大鼠认知功能减退,丙戊酸钠能够促进致痫大鼠学习与记忆获取能力。各组大鼠海马组织GABABR蛋白相对表达量检测显示,致痫大鼠较正常大鼠GABABR蛋白相对表达量明显降低;与致痫组大鼠相对比,丙戊酸钠组GABABR蛋白相对表达量增高。结论丙戊酸钠可以提高致痫大鼠GABABR表达从而达到抗癫痫作用,还可以改善致痫大鼠的认知功能。

ObjectiveTo study the effect of sodium valproate on GABAB receptor in hippocampus of pilocarpine induced kindled rats model and effects on cognitive function.MethodsKindled rats were induced by pilocarpine,and the rats were randomly divided into four groups(Normal Group,Sodium Valproate Group,normal saline Group,Kindled Epilepsy Group),and the cognitive function was evaluated by using water maze and avoid dark test.The expression of GABAB receptor was tested by immunohistochemical staining,RT-PCR and Western Blot.ResultsAvoid dark test:Normal,Sodium Valproate,Normal saline and Kindled group shuttle times were respectively 6.8±0.6,5.2±0.3,3.4±0.3 and 3.6±0.3.The darkroom incubation period were respectively 26.1±3.4,62.2±6.9,92.8±8.3 and 91.2±9.1,and the water maze test showed the same trend.Compared with normal rats,the results showed that cognitive function was decreased in epileptogenic rats.And valproate promoted the learning and memory acquisition ability of epileptogenic rats.Induced epilepsy group expressed significantly lower GABAB receptor levels than that in normal group;Induced epilepsy group showed higher expression of GABAB receptor.ConclusionSodium valproate could inhibit the seizure in pilocarpine induced kindling rats by increasing the expression GABAB receptor level in hippocampus of rat,and it also can improve cognitive function in pilocarpine induced kindling rats.