茸菖胶囊预处理对致痫大鼠血脑屏障超微结构及闭锁蛋白-5的影响

Effects of Rongchang Capsule Pretreatment on Blood Brain Barrier and Claudin-5 in Epileptic Rats

目的观察茸菖胶囊预处理对癫痫大鼠血脑屏障(BBB)超微结构及闭锁蛋白-5(claudin-5)的影响。方法将60只SD大鼠随机分为正常组、模型组、西药组、中药低剂量预处理组(中低组)、中药中剂量预处理组(中中组)和中药高剂量预处理组(中高组) 6组,每组10只。采用PTZ慢性点燃动物模型,茸菖胶囊预处理即采用造模同时分别予以各组相应的中西药药液预处理干预,预处理剂量分别为治疗量的1/2,2次/d,1次/d,连续28 d。预处理后各组均予相应治疗量继续治疗28 d。电镜观察各组大鼠海马BBB超微结构,伊文思蓝(EB)法观察海马BBB通透性及免疫组化法测定claudin-5表达。结果电镜下中药各组大鼠海马BBB超微结构损伤程度均低于模型组,中药各组和西药组海马EB浓度均低于模型组(P<0.05);中药各组大鼠海马EB浓度表达与西药组比较,差异无统计学意义(P>0.05);中药各组和西药组大鼠海马claudin-5表达均低于模型组(P<0.05),中低组大鼠海马claudin-5表达低于西药组(P<0.05),中中组和中高组与西药组比较,差异无统计学意义(P>0.05)。推测从而达到改善癫痫大鼠认知功能的作用。结论通过茸菖胶囊预处给药的方法,可能通过降低claudin-5蛋白表达修复海马BBB超微结构,改善海马记忆功能。

Objective To observe the effect of Rongchang Capsule pretreatment on blood brain barrier(BBB) and claudin-5 in epileptic rats.Methods Sixty SD rats were randomly divided into normal group,model group,western medicine group,middle-low dose group,middle-middle dose group and middle-high dose group with 10 rats in each group.PTZ chronic kindling animal model was adopted.Rongchang Capsule was pretreated with the corresponding Chinese and western medicine solution of each group at the same time of modeling.The pretreatment dose was 1/2 of the therapeutic dose,twice a day,once a day for 28 consecutive days.After pretreatment,each group was given the corresponding treatment amount and continued treatment for 28 days.Electron microscopy was used to observe the ultrastructure of BBB in hippocampus of rats in each group.Evans blue(EB) method was used to observe the permeability of BBB in hippocampus and immunohistochemical method was used to determine the expression of claudin-5.Results Under the electron microscope,the damage degree of BBB ultrastructure in hippocampus of rats in each group of traditional Chinese medicine was lower than that in the model group,and the EB concentration in hippocampus in each group of traditional Chinese medicine and western medicine was lower than that in the model group(P<0.05).There was no significant difference in EB concentration expression in hippocampus between Chinese medicine groups and western medicine groups(P>0.05).The expression of claudin-5 in hippocampus of rats in traditional Chinese medicine group and western medicine group was lower than that in the model group(P<0.05),while the expression of claudin-5 in hippocampus of rats in the middle-low dose group was lower than that in the western medicine group(P<0.05).There was no significant difference between middle-middle dose group and middle-high dose group(P>0.05).Presumably,it can improve the cognitive function of epileptic rats.Conclusion Through the pre-administration of Rongchang Capsule,it is possible to repair the ultrastructure of hippocampus BBB and improve the hippocampus memory function by reducing the expression of claudin-5 protein.