不同剂量天麻素对甲基苯丙胺依赖CPP大鼠海马中TLR4/MyD88/NF-κB炎症信号通路的影响  

Effects of Different Doses of Gastrodin on TLR4/MyD88/NF-κB Inflammatory Signal Pathway in Hippocampus of Methamphetamine Dependent CPP Rats

作　　者：朱婷娜 曹媛媛 张园 刘鹏亮 王一航 吴亚梅 李利华 赵永娜 洪仕君 ZHU Tingna;CAO Yuanyuan;ZHANG Yuan;LIU Pengliang;WANG Yihang;WU Yamei;LI Lihua;ZHAO Yongna;HONG Shijun(School of Pharmaceutical Sciences&Yunnan Key Laboratory of Pharmacology for Natural Products,Kunming Medical University,Kunming,Yunnan 650500;School of Pharmaceutical Sciences School of Forensic Medicine,Kunming Medical University,Kunming,Yunnan 650500;School of Pharmaceutical Sciences School of International Education,Kunming Medical University,Kunming,Yunnan 650500;Yunnan Institute for Food and Drug Contral,Kunming Yunnan 650106,China)

机构地区：[1]昆明医科大学药学院暨云南省天然药物药理重点实验室,云南昆明650500 [2]昆明医科大学法医学院,云南昆明650500 [3]昆明医科大学国际教育学院,云南昆明650500 [4]云南省食品药品监督检验研究院,云南昆明650106

出　　处：《昆明医科大学学报》2023年第2期33-39,共7页Journal of Kunming Medical University

基　　金：国家自然科学基金资助项目(81760337);云南省科技厅-昆明医科大学应用基础研究联合专项基金资助项目[2019FE001(-163)]。

摘　　要：目的探讨不同剂量的天麻素(Gastrodin,Gas)对甲基苯丙胺(Methamphetamine,Meth)依赖条件性位置偏爱(Conditioned place preference,CPP)大鼠海马中TLR4/MyD88/NF-κB通路的作用。方法建立Meth(10 mg/kg,ip,14 d)依赖大鼠CPP模型,采用低中高剂量的天麻素(10、30、100 mg/kg)干预14 d后,采用Western blotting和RT-qPCR方法检测TLR4/MyD88/NF-κB信号通路中关键因子的蛋白和mRNA在海马中的表达水平。结果天麻素干预后TLR4、MyD88、NF-κB p65、TRAF6的蛋白和mRNA表达呈剂量依赖性降低(P<0.001、P<0.01或P<0.05)、p-NF-κB p65的蛋白表达呈剂量依赖性降低(P<0.01或P<0.05)、IκB-α的蛋白和mRNA表达呈剂量依赖性升高(P<0.01或P<0.05),天麻素干预后p-IκB-α的蛋白表达降低(P<0.01)。结论天麻素干预对甲基苯丙胺依赖CPP大鼠海马的神经炎症具有保护作用,且与TLR4/MyD88/NF-κB信号通路密切相关。Objective To investigate the effects of different dosages of gastrodin onTLR4/MyD88/NF-κB signal pathway in the hippocampus of methamphetamine(meth)dependence rats. Methods The conditioned place preference(CPP) model of meth was established,meth(10mg/kg) was administered(i.p,14 d),and then,different dosages(10,30,100 mg/kg) of gastrodin were used to intervene in 14 days. Western blotting and RTqPCR were used to explore the expression level of protein and mRNA of key factors in TLR4/MyD88/NF-κB signal pathway in hippocampus. Results Gastrodin decreased the protein and mRNA expression of TLR4,MyD88,TRAF6, NF-κBp65 in a dose-dependent manner(P < 0.001,P < 0.01 or P < 0.05),and the protein expression of p-NF-κB p65 was reduced with showing a significant dose-response relationship( P < 0.01 or P < 0.05).Gastrodin increased the protein and mRNA expression of IκB-α with showing a significant dose-response relationship( P < 0.01 or P < 0.05). Gastrodin reduced the protein expression of p-IκB-α( P < 0.01).Conclusion Gastrodin intervention has a protective effect against hippocampal neuroinflammation in methamphetamine-dependent CPP rats, and is closely related to the function of TLR4/MyD88/NF-κB signal pathway.

关 键 词：甲基苯丙胺依赖 条件性位置偏爱 海马 天麻素 TLR4/MyD88/NF-κB信号转导通路 

分 类 号：R964[医药卫生—药理学]