甘草苷通过TLR4/IL-6信号通路改善癫痫幼鼠认知功能及海马神经元损伤  

Liquiritin improves cognitive function and hippocampal neuron damage of young rats with epilepsy via TLR4/IL-6 signaling pathway

作　　者：赵学廉[1] 方敬献[1] 朱洋洋 武跃辉[2] Zhao Xuelian;Fang Jingxian;Zhu Yangyang;Wu Yuehui(Nanyang First People's Hospital,Nanyang 473000,Henan,China)

机构地区：[1]南阳市第一人民医院,河南南阳473000 [2]郑州大学第五附属医院,河南郑州450000

出　　处：《临床心身疾病杂志》2024年第5期1-6,共6页Journal of Clinical Psychosomatic Diseases

基　　金：河南省医学科技攻关计划联合共建项目(编号LHGJ20190418)。

摘　　要：目的探讨甘草苷改善癫痫幼鼠认知功能、海马神经元损伤及对Toll样受体4(TLR4)/白细胞介素-6(IL-6)信号通路的调节作用。方法将60只幼鼠随机分为正常组、模型组、甘草苷组、激动剂组和激动剂+甘草苷组,每组12只。除正常组外,其余组幼鼠腹腔注射氯化锂-匹罗卡品建立癫痫模型。采用水迷宫实验检测幼鼠认知功能,酶联免疫吸附法检测血清IL-1β、肿瘤坏死因子α(TNF-α)和高迁移率族蛋白B1(HMGB1)水平,苏木精-伊红染色法观察海马神经元组织病理形态,末端脱氧核苷酸转移酶介导的dUTP标记测定法检测海马神经元凋亡率,蛋白印迹法检测海马B淋巴细胞瘤-2基因(Bcl-2)、Bcl-2相关X蛋白(Bax)、TLR4、IL-6、IL-1β、TNF-α和HMGB1蛋白表达水平。结果模型组和激动剂组幼鼠海马神经元形态不规则,排列紊乱,细胞核固缩、碎裂,细胞数减少,甘草苷组和激动剂+甘草苷组幼鼠海马神经元损伤程度明显改善。与模型组比较,甘草苷组幼鼠逃避潜伏期缩短,穿越平台次数增加,血清IL-1β、TNF-α和HMGB1表达水平,海马神经元凋亡率以及Bax、TLR4、IL-6、IL-1β、TNF-α和HMGB1蛋白表达水平均降低,Bcl-2蛋白表达水平升高(P<0.05);与激动剂组比较,激动剂+甘草苷组幼鼠逃避潜伏期缩短,穿越平台次数增加,血清IL-1β、TNF-α和HMGB1表达水平,海马神经元凋亡率以及Bax、TLR4、IL-6、IL-1β、TNF-α和HMGB1蛋白表达水平均降低,Bcl-2蛋白表达水平升高(P<0.05)。结论甘草苷可减轻癫痫幼鼠炎症反应,降低神经元损伤程度,改善认知功能和空间记忆能力。甘草苷可能是通过抑制TLR4/IL-6信号通路发挥作用。Objective To explore the effects of liquiritin improving cognitive function and hippocampal neuron damage of young rats with epilepsy and its moderating effects on Toll-like receptor4/interleukin-6(TLR4/IL-6)signaling pathway.Methods Sixty young rats were randomly divided into normal,model,liquiritin,agonist,and agonist+liquiritin group with 12 ones in each.Except normal group,the rats in other groups were intraperitoneally injected with lithium chloride-pilocarpine to establish epilepsy model.The cognitive functions of young rats were detected using water maze test,the levels of serum IL-1β,tumor necrosis factorα(TNF-α)and high mobility group protein B1(HMGB1)done using enzyme-linked immunosorbent assay(ELISA),the pathomorphisms of hippocampus neuronal tissues observed by hematoxylin-eosin(HE)staining,the apoptosis rates of hippocampal neurons detected using terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling(TUNEL),and the expression levels of B lymphoblastoma 2 gene(Bcl-2)、Bcl-2 associated X protein(Bax),TLR4,IL-6,IL-1β,TNF-αand HMGB1 in hippocampus done using western blot.Results The morphology of hippocampal neuron of young rat was irregular,arrangement disordered,the nucleus shrunk and broken,and the number of cells reduced in model and agonist group,hippocampus neuronal damage notably improved in liquiritin and agonist+liquiritin group.Compared with model group,the escape latency shortened,platform crossing times increased,serum IL-1β,TNF-αand HMGB1expression level,apoptosis rate of hippocampal neurons as well as protein expression levels of Bax,TLR4,IL-6,IL-1β,TNF-αand HMGB1 lowered,and Bcl-2 protein expression increased in liquiritin group(P<0.05).Compared with agonist group,the escape latency shortened,platform crossing times increased,serum IL-1β,TNF-αand HMGBlexpression level,apoptosis rate of hippocampal neurons as well as protein expression levels of Bax,TLR4,IL-6,IL-1β,TNF-αand HMGB1 lowered,and Bcl-2 protein expression increased in agonist+liquiritin group(P<0.05).

关 键 词：甘草苷 癫痫 神经元 认知功能 Toll样受体4/白细胞介素-6信号通路 

分 类 号：R742.1[医药卫生—神经病学与精神病学] R965[医药卫生—临床医学]