天麻钩藤饮通过抑制p38 MAPK/NF-κB信号通路对PILO诱导小鼠癫痫模型的神经保护作用  

Neuroprotective Effect of Tianma Hooker Drink on PILO-induced Epilepsy Model in Mice by Inhibiting p38 MAPK/NF-κB Signaling Pathway

作　　者：施晓宇 陈群[2] 李可心 冯大庆 王文增 陈宏[3] SHI Xiaoyu;CHEN Qun;LI Kexin(Heilongjiang University of Chinese Medicine,Heilongjiang 150040,China)

机构地区：[1]黑龙江中医药大学,哈尔滨150006 [2]哈尔滨市阿城区人民医院检验科,150030 [3]黑龙江中医药大学附属第一医院,哈尔滨150030

出　　处：《医学研究杂志》2025年第3期68-72,79,共6页Journal of Medical Research

基　　金：中国博士后科学基金第13批特别资助项目(2020T130178)。

摘　　要：目的探讨天麻钩藤饮通过抑制p38丝裂原活化蛋白激酶(p38mitogen-activated protein kinase,p38 MAPK)/核转录因子-κB(nuclear transcription factor-κB,NF-κB)信号通路对小鼠癫痫(epilepsy,EP)模型的神经保护作用。方法选取40只雄性昆明小鼠,将其按照随机数字表法分为对照组、模型组、天麻钩藤饮高剂量组和天麻钩藤饮低剂量组,每组各10只。造模前1周,各组分别给予相应药物灌胃。通过盐酸匹罗卡品(pilocarpine,PILO)构建小鼠急性EP模型。评估小鼠行为学及脑电图情况;原位末端转移酶标记技术(terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling,TUNEL)检测各组小鼠海马组织凋亡细胞率;酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测血清中的超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)水平和海马组织中的肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)水平;Western blot法测量海马组织中p38 MAPK和磷酸化核转录因子-κB(phosphorylated nuclear factor kappa B,p-NF-κB)的蛋白表达水平。结果与对照组比较,模型组小鼠脑电图可见连续痫样波,其尖波、棘波、棘慢波明显增多,EP发作频率、持续时间、发作级别均增加(P<0.01);海马组织神经元凋亡率显著升高(P<0.01);血清中SOD水平降低、MDA水平增加(P<0.05);海马组织中TNF-α、IL-6、p38 MAPK和p-NF-κB p65蛋白表达水平升高(P<0.05)。与模型组比较,天麻钩藤饮高、低剂量组小鼠脑电图痫性波频率及强度明显减少,EP发作频率、持续时间和发作级别均减少(P<0.05);海马组织中神经元凋亡率均减少(P<0.05);血清中SOD水平增加、MDA水平降低(P<0.05);海马组织中TNF-α、IL-6、p38 MAPK、p-NF-κB p65蛋白表达水平降低(P<0.05)。结论天麻钩藤饮可能通过抑制p38 MAPK/NF-κB信号通路发挥抗EP的作用。Objective To investigate the neuroprotective effect of tianma hookteng drink on mice epilepsy(EP)model by inhibiting p38mitogen-activated protein kinase(p38 MAPK)/nuclear transcription factor-κB(NF-κB)signaling pathway.Methods Forty male Kunming mice were randomly divided into four groups:control group,model group,high-dose tianma hooker drink group and low-dose of tianma hooker drink group according to random number table method,with 10mice in each group.One week before modeling,the mice in each group was given the appropriate drugs by gavage.Acute EP model in mice was constructed by pilocarpine hydrochloride.The behavioral performance and electroencephalogram(EEG)in mice were evaluated;terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)staining method was applied to detect the number of apoptotic cells in hippocampal tissue of mice in each group;enzyme-linked immunosorbent assay(ELISA)was used to detect the superoxide dismutase(SOD)and malondialdehyde(MDA)levels in serum and tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)levels in hippocampal tissues;Western blot method was used to detect the protein expression levels of p38 MAPK and phosphorylated nuclear factor kappa B(p-NF-κB)in hippocampal tissue.Results Compared with the control group,continuous epileptiform waves were seen in the EEG of mice in the model group,with a significant increase in the number of spikes,spindles,and spindles-slow waves,and an increase in EP seizure frequency,duration,and seizure level(P<0.01);neuronal apoptosis rate in hippocampal tissues was significantly elevated(P<0.01);the level of SOD in serum was decreased,and the level of MDA was increased(P<0.05);the expression levels of TNF-α,IL-6 and the protein expression levels of p38 MAPK and p-NF-κB p65 were elevated in hippocampal tissue(P<0.05).Compared with the model group,the frequency and intensity of epileptic waves in the EEG of mice in the high-dose and low-dose groups of tianma hooker drink were significantly reduced,and the frequency,du

关 键 词：天麻钩藤饮 p38 MAPK p-NF-κB 癫痫模型小鼠 神经保护 

分 类 号：R256.2[医药卫生—中医内科学]