转位蛋白18KDA介导葛根素抗创伤后应激性障碍作用机制研究  

Role of Translocation Protein 18KDA in the Treatment of Post-Traumatic Stress Disorder by Puerarin

作　　者：招志辉[1] 李霭燕 关彩华 ZHAO Zhihui;LI Aiyan;GUAN Caihua(Department of Pharmacy,the First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzho1u510405;Department of Pharmacy,Panyu Hospital of Traditional Chinese Medicine,Guangzhou 511400)

机构地区：[1]广州中医药大学第一附属医院药学部,广州510405 [2]广州市番禺区中医院药学部,广州511400

出　　处：《中药药理与临床》2023年第11期57-62,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：广东省中医药局科研项目(编号:20201096)。

摘　　要：目的:探讨转位蛋白18KDA(TSPO)介导葛根素抗创伤后应激性障碍的作用。方法:构建创伤后应激性障碍大鼠模型,将成功建模大鼠随机分为模型对照组、舍曲林15 mg/kg组、葛根素5、10、20 mg/kg组,另设置假手术对照组,每组10只大鼠。各组分别灌胃给予相应药物或蒸馏水,1次/d,持续2 w。末次给药24 h后,分别采用高架十字迷宫试验、环境惊恐试验检测大鼠行为学变化;ELISA法检测前额皮层、海马体、杏仁核和血小板中四氢孕酮含量;全细胞膜片钳记录脑片γ-氨基丁酸A型受体(GABAA)抑制性突触后电流(IPSC);RT-qPCR法和Western blot法检测前额皮层、海马体、杏仁核中Tspo mRNA和蛋白表达。结果:与假手术对照组比较,模型对照组大鼠进入开臂时间比和进入开臂停留次数比显著减少,僵住时间显著增加(P<0.01);前额皮层、海马体、杏仁核中Tspo mRNA和蛋白表达显著下调,前额皮层、海马体、杏仁核和血小板中四氢孕酮含量显著减少(P<0.01),前额皮层、海马体、杏仁核IPSC幅度与频率显著下降(P<0.01);与模型对照组比较,各给药组大鼠进入开臂时间比和进入开臂停留次数比显著增加(P<0.01),僵住时间明显减少(P<0.05或P<0.01);前额皮层、海马体、杏仁核中Tspo mRNA和蛋白表达明显上调,前额皮层、海马体、杏仁核和血小板中四氢孕酮含量明显增加(P<0.05或P<0.01),前额皮层、海马体、杏仁核IPSC幅度与频率明显增加(P<0.05或P<0.01)。结论:葛根素可发挥抗创伤后应激性障碍功能,可能与其促进大鼠脑部TSPO表达,升高四氢孕酮含量,提高GABAAIPSC幅度与频率相关。Objective:To investigate the role of translocation protein 18KDA(TSPO)in the treatment of post-traumatic stress disorder(PTSD)by puerarin.Methods:The rat model of PTSD was established.The successfully modeled rats were randomized into model control,sertraline(15 mg/kg),and puerarin(5,10,and 20 mg/kg)groups(n=10),and a sham operation group(n=10)was set up.Rats in all the groups were administrated with corresponding drugs or saline water once per day for 2 weeks.The behavioral changes of rats in each group were examined by elevated cross maze test and fear conditioning test 24 h after the last administration.Enzyme-linked immunosorbent assay(ELISA)was employed to measure the levels of allopregnanolone in the prefrontal cortex,hippocampus,amygdala,and platelets.The whole cell patch clamp was used to recordγ-aminobutyric acid type A receptor(GABA_A)inhibitory postsynaptic current(IPSC)in brain slices.Real time quantitative polymerase chain reaction(RT-qPCR)and western blot(WB)were employed to determine the mRNA and protein levels of TSPO in the prefrontal cortex,hippocampus,and amygdala.Results:Compared with the sham operation group,the modeling of PTSD decreased the time spent in the open arm and number of entries in the open arm and increased the immobile time(P<0.01).Compared with the model control group,sertraline and puerarin increased the time spent in the open arm and the number of entries in the open arm(P<0.01)and reduced the immobile time(P<0.05 or P<0.01).Compared with the sham operation group,the modeling down-regulated the mRNA and protein levels of TSPO in the prefrontal cortex,hippocampus,and amygdala,lowered the levels of allopregnanolone in the prefrontal cortex,hippocampus,amygdala,and platelets(P<0.01),and decreased amplitude and frequency of IPSC in the prefrontal cortex,hippocampus,and amygdala(P<0.01).Compared with the model control group,sertraline and puerarin up-regulated the mRNA and protein levels of TSPO in the prefrontal cortex,hippocampus,and amygdala,elevated the levels of allopregnano

关 键 词：葛根素 创伤后应激性障碍 18KDA转位蛋白 突触后电流 

分 类 号：R285.5[医药卫生—中药学]