摘要
目的:探讨平肝止痫复方联合卡马西平对难治性癫痫大鼠神经元损伤的作用及机制。方法:将海人酸和苯妥英钠诱导制备的难治性癫痫大鼠分成模型组、卡马西平组、平肝止痫复方联合卡马西平组,另设假手术组。各组大鼠给予药物或生理盐水灌胃,每天1次,连续给药28 d后采用苏木素-伊红(HE)染色检测大鼠海马病理变化;ELISA试剂盒检测大鼠血清中IL-1β、IL-6、TNF-α和TGF-β1的含量;TUNEL法观察海马组织的凋亡变化;qPCR及IHC法检测海马组织中高迁移率族蛋白B1(HMGB1)、核因子κB(NF-κB)和Toll样受体4(TLR4)的mRNA及蛋白表达变化。结果:与模型组相比,卡马西平组及联合用药组大鼠海马组织病理损伤减轻及细胞凋亡率下降,HMGB1、TLR4和NF-κB的表达量均显著下降(P<0.05),大鼠血清中IL-1β、IL-6和TNF-α的含量均显著下降,TGF-β1的含量则显著增加(P<0.05);与卡马西平组比较,联合用药组大鼠海马组织病理损伤减轻,细胞凋亡率显著下降(P<0.05),HMGB1、TLR4和NF-κB的表达量也均下降,血清中IL-1β、IL-6和TNF-α含量均下降,TGF-β1含量则显著增加(P<0.05)。结论:平肝止痫复方联合卡马西平对难治性癫痫大鼠神经元有保护作用,其具体机制可能与调节HMGB1/TLR4/NF-κB通路抑制炎症反应有关。
Objective:To study the effect and mechanism of Pinggan Zhixian compound medicine combined with carbamaze-pine on neuronal damage in intractable epilepsy rats.Methods:The intractable epilepsy model rats induced by kainic acid and phenyt-oin sodium were divided into model group,carbamazepine(CBZ)group,Pinggan Zhixian compound combined with carbamazepine(PGZX+CBZ)group,and sham operation group.Rats in each group were given corresponding drugs for 28 days and then hematoxylineosin(HE)staining was used to observe the pathological changes of hippocampus;the contents of IL-1β,IL-6,TNF-αand TGF-β1 in rat serum were detected by ELISA kit;the apoptosis of hippocampal neurons was detected by TUNEL;the expression levels of HMGB1,TLR4 and NF-κB were detected by qPCR and IHC.Results:Compared with the model group,the pathological damage of hippocampus in carbamazepine group and Pinggan Zhixian compound combined with carbamazepine group was reduced,the apoptosis rate was decreased,the expression of HMGB1,TLR4,NF-κB was also significantly decreased(P<0.05),the contents of IL-1β,IL-6,TNF-αin serum were significantly decreased,and the content of TGF-β1 was significantly increased(P<0.05).Compared with the carbamazepine group,the pathological damage of hippocampus in carbamazepine group and Pinggan Zhixian compound combined with carbamazepine group was reduced,the apoptosis rate was decreased,the expression of HMGB1,TLR4,NF-κB was also significantly decreased(P<0.05),the contents of IL-1β,IL-6,TNF-αin serum were significantly decreased,and the content of TGF-β1 was sig-nificantly increased(P<0.05).Conclusion:Pinggan Zhixian compound medicine combined with carbamazepine has protective effect on neurons of intractable epilepsy rats,and its specific mechanism may be related to regulating HMGB1/TLR4/NF-κB signal pathway and inhibiting inflammation.
作者
刘运权
李若照
郭磊磊
娄金波
姚娟
安运佳
熊保月
王强
LIU Yun-Quan;LI Ruo-Zhao;GUO Lei-Lei;LOU Jin-Bo;YAO Juan;AN Yun-Jia;XIONG Bao-Yue;WANGQiang(The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550000,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2021年第19期2345-2350,共6页
Chinese Journal of Immunology
基金
国家自然科学基金项目(81760857)
黔科合平台人才项目([2018]5605)资助。
