天麻素治疗缺血性脑卒中导致神经元死亡的作用机制研究  

Study on mechanism of gastrodin in treatment of neuronal death caused by ischemic stroke

作　　者：许鑫 周欣 楚世峰 李芳芳 郑清炼 何宏媛 陈乃宏 XU Xin;ZHOU Xin;CHU Shi-feng;LI Fang-fang;ZHENG Qing-lian;HE Hong-yuan;CHEN Nai-hong(Institute for Brain Research and Rehabilitation,South China Normal University,Guangzhou 510631,China;State Key Lab of Bioactive Substances and Functions of Natural Medicines,Institute of Materia Medica&Neuroscience Center,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China;Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China)

机构地区：[1]华南师范大学脑科学与康复医学研究院,广东广州510631 [2]中国医学科学院药物研究所神经科学中心,天然药物活性物质与功能国家重点实验室,北京100050 [3]天津中医药大学,天津301617

出　　处：《中国药理学通报》2020年第11期1581-1587,共7页Chinese Pharmacological Bulletin

基　　金：北京市自然科学基金资助项目(No 7192135);国家自然科学基金资助项目(No 81730096);国家“重大新药创制”科技重大专项(No 2018ZX09711001-002-007、2018ZX09711001-003-005、2018ZX09711001-009-013);中国医学科学院医学与健康科技创新工程经费资助(No 2016-12M-1-004)。

摘　　要：目的研究天麻素(gastrodin,Gas)对缺血性脑卒中导致神经元死亡的作用机制。方法通过线栓法建立短暂性局部脑缺血/再灌注大鼠模型,实验动物分为假手术组、模型组、Gas低剂量组(25 mg·kg^-1)、Gas中剂量组(50 mg·kg^-1)、Gas高剂量组(100 mg·kg^-1)和依达拉奉组(10 mg·kg^-1)。给药3 d后,TTC染色检测脑梗死和水肿;Zea Longa评分评估神经受损程度;尼氏染色检测神经元形态变化;Western blot检测caspase-3、caspase-8和Survivin、HBXIP蛋白的表达;免疫荧光染色法检测Survivin和HBXIP的表达。结果与假手术组相比,模型组3 d后神经功能严重缺损,脑梗死和水肿增加,尼氏小体减少,活化的caspase-3和caspase-8表达增加(P<0.05),Survivin和HBXIP表达增加;与模型组相比,Gas组和依达拉奉组神经功能缺损减轻,caspase-3和caspase-8蛋白表达减少(P<0.01),Survivin和HBXIP表达增加,抑制神经元死亡。结论Gas可通过促进抗凋亡蛋白表达和抑制caspase介导的神经元死亡,从而改善缺血性脑卒中。Aim To study the mechanism of gastrodin on neuronal death caused by ischemic stroke.Methods In this study,the rat model of transient local cerebral ischemia/reperfusion was established by thread bolt method.The experimental animals were divided into sham operation group,model group,gastrodin low dose group(25 mg·kg^-1),gastrodin medium dose group(50 mg·kg^-1),gastrodin high dose group(100 mg·kg^-1)and edaravone group(10 mg·kg^-1).After 3 days of administration,TTC staining was used to detect cerebral infarction and edema.Zea Longa score was used to evaluate the degree of nerve damage.Nissl staining was used to detect morphological changes of neurons.Western blot was used to detect the expression of caspase-3,caspase-8.Fluorescence staining was used to detect the expression of Survivin and HBXIP.Results Compared with sham group,the model group had severe neurological deficits,increased cerebral infarction and edema,decreased nisei corpuscle,increased expression of activated caspase-3 and caspase-8(P<0.05),and increased expression of Survivin and HBXIP in model group after 3 days.Compared with model group,the neurological deficit was reduced after 3 days in gastrodin group and edaravone group,the expression of activated caspase-3 and caspase-8 protein decreased(P<0.01),the expression of Survivin and HBXIP increased,and neuronal death was suppressed.Conclusions Gastrodin can improve ischemic stroke by promoting the expression of anti-apoptotic proteins and inhibiting caspase-mediated neuronal death.

关 键 词：天麻素 缺血/再灌注 脑卒中 神经元死亡 SURVIVIN HBXIP 

分 类 号：R-332[医药卫生] R284.1