天麻素对戊四氮致痫模型大鼠的治疗作用及对细胞自噬、凋亡机制的研究  

Therapeutic effect of gastrodin on pentylenetetrazol-induced epilepsy model rats and its mechanism of autophagy and apoptosis

作　　者：翁柠 况时祥 薛红 何前松 王强 刘建辉 赵芝兰 李艳 Weng Ning;Kuang Shixiang;Xue Hong;He Qiansong;Wang Qiang;Liu Jianhui;Zhao Zhilan;Li Yan(Department of Neurology, the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guizhou Province,Guiyang 550003, China)

机构地区：[1]贵州中医药大学第二附属医院神经内科,贵阳550003

出　　处：《疑难病杂志》2021年第1期77-82,共6页Chinese Journal of Difficult and Complicated Cases

基　　金：贵州省科技计划项目[黔科合LH字(2016)7130号]。

摘　　要：目的探讨天麻素对戊四氮致痫模型大鼠的治疗作用及对细胞自噬、凋亡机制的研究。方法2018年11月—2019年11月于贵州中医药大学实验室进行实验。将Wistar雄性大鼠以戊四氮(PTZ)32 mg·kg^(-1)·d^(-1)腹腔注射诱导癫痫模型,通过筛选将造模成功的100只大鼠按随机数字表法分为戊四氮致痫模型组、丙戊酸钠(VPA)干预组、天麻素小剂量干预组、天麻素中剂量干预组、天麻素大剂量干预组,每组20只,另纳入20只大鼠为正常对照组,共120只。造模成功后天麻素小、中、大剂量干预组分别予大鼠腹腔注射天麻素30、60、120 mg·kg^(-1)·d^(-1),丙戊酸钠干预组予大鼠腹腔内注射丙戊酸钠120 mg·kg^(-1)·d^(-1)。治疗2周后用免疫组化染色及蛋白印迹法检测大鼠海马组织LC3、Beclin1、Bax、Caspase-3表达及检测大鼠海马区细胞凋亡率。结果与正常对照组比较,模型组LC3、Bax、Beclin1、Caspase-3水平均升高,差异有统计学意义(P<0.05);天麻素各剂量组及丙戊酸钠干预组LC3、Beclin1、Bax、Caspase-3表达均低于模型组(P<0.05),天麻素小、中剂量组LC3、Bax、Beclin1、Caspase-3表达均高于天麻素大剂量组及丙戊酸钠干预组(P<0.05),天麻素大剂量组与丙戊酸钠干预组表达比较差异无统计学意义(P>0.05)。与正常对照组比较,模型组海马区细胞凋亡率升高,差异有统计学意义(P<0.05);天麻素各剂量组及丙戊酸钠干预组海马区细胞凋亡率均低于模型组(P<0.05),且天麻素大剂量组大鼠海马区细胞凋亡率低于天麻素小剂量组和天麻素中剂量组,差异均具有统计学意义(P<0.05),天麻素大剂量组海马区凋亡率与丙戊酸钠干预组比较差异无统计学意义(P>0.05)。结论天麻素能通过调控戊四氮致痫模型大鼠海马区LC3、Bax、Caspase3、Beclin1等表达,抑制大鼠海马区细胞凋亡、自噬,抑制癫痫发作。Objective To explore the therapeutic effect of gastrodin on pentylenetetrazol-induced epilepsy model rats and the study on the mechanism of autophagy and apoptosis.Methods From November 2018 to November 2019,the experiment was conducted in the Laboratory of Guizhou University of Traditional Chinese Medicine.Wistar male rats were injected intraperitoneally with pentylenetetrazol(PTZ)32 mg·kg^(-1)·d^(-1) to induce epilepsy models.After screening,100 rats that were successfully modeled were divided into pentylenetetrazole induced by a random number table.Epilepsy model group,sodium valproate(VPA)intervention group,low-dose gastrodin intervention group,medium-dose gastrodin intervention group,high-dose gastrodin intervention group,20 rats in each group,and 20 rats were included as normal control group,A total of 120.After successful modeling,the small,medium,and high-dose gastrodin intervention groups were given intraperitoneal injections of gastrodin 30,60,and 120 mg·kg^(-1)·d^(-1),respectively.The sodium valproate intervention group was given intraperitoneal injections of C Sodium valerate 120 mg·kg^(-1)·d^(-1).After 2 weeks of treatment,immunohistochemical staining and western blotting were used to detect the expression of LC3,Beclin1,Bax,and Caspase-3 in rat hippocampus,and to detect the apoptosis rate of rat hippocampus.Results Compared with the normal control group,the LC3,Bax,Beclin1,and Caspase-3 levels in the model group increased with statistical significance(P<0.05);Each dose group of gastrodin and the sodium valproate intervention group LC3,Beclin1,Bax and Caspase-3 were lower than those of the model group(P<0.05).The expressions of LC3,Bax,Beclin1 and Caspase-3 in the small and medium-dose gastrodin group were higher than those in the high-dose gastrodin group and the sodium valproate intervention group(P<0.05).There was no significant difference in expression between the high-dose gastrodin group and the sodium valproate intervention group(P>0.05).Compared with the normal control group,the hippoca

关 键 词：癫痫 天麻素 自噬 凋亡 大鼠 

分 类 号：R742.1[医药卫生—神经病学与精神病学]