冰片配伍黄芪甲苷与三七总皂苷对脑缺血/再灌注后血脑屏障通透性的影响  

Effect of borneol combined with astragaloside IV and Panax notoginseng saponins on permeability of blood-brain barrier after cerebral ischemia-reperfusion

作　　者：丁煌[1] 唐三 杨筱倩[1] 刘晓丹[1] 黄小平[1] 邓常清[1] DING Huang;TANG San;YANG Xiao-qian;LIU Xiao-dan;HUANG Xiao-ping;DENG Chang-qing(Molecular Pathology Lab, Key Lab of Hunan Province for Prevention and Treatment of Integrated Traditional Chinese andWestern Medicine on Cardio-cerebral Diseases, Key Lab of Hunan Universities for Cell Biology and Molecular Techniques,Hunan University of Chinese Medicine, Changsha 410208, China)

机构地区：[1]湖南中医药大学分子病理实验室中西医结合心脑疾病防治湖南省重点实验室细胞生物学与分子技术湖南省高校重点实验室

出　　处：《中国药理学通报》2019年第11期1516-1523,共8页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81573875);湖南省科技厅科技创新平台与人才计划-中医脑病临床研究中心(No 2017SK4005);“中西医结合防治心脑血管疾病的相关基础研究”;“中医药防治心脑血管疾病基础研究”湖南省自然科学创新群体基金;湖南中医药大学“十三五”一级学科基础医学建设项目(No 06);湖南省教育厅一般项目(No 18C0407)

摘　　要：目的 探讨冰片、黄芪甲苷(AST Ⅳ)和三七总皂苷(PNS)配伍对脑缺血/再灌注后血脑屏障(BBB)的影响。方法 脑缺血/再灌注大鼠灌胃给药,观察神经功能缺损症状,测定脑组织含水量和BBB通透性、闭锁小带蛋白1(ZO-1)、ZO-2、咬合蛋白(Occludin)及闭合蛋白5(Claudin-5)表达。结果 脑缺血/再灌注后,大鼠出现神经功能缺损症状,神经功能评分和脑含水量增加,BBB破坏。各药物能不同程度减轻上述病理改变,冰片+AST Ⅳ+PNS效应最强,优于药物单用及AST Ⅳ+PNS。脑缺血/再灌注后,ZO-1、ZO-2、Occludin、Claudin-5表达减少。各药物使ZO-1增加,除AST Ⅳ外,上调Occludin表达;冰片+AST Ⅳ+PNS还明显上调ZO-2,且上调ZO-1、ZO-2、Occludin的效应优于药物单用及AST Ⅳ+PNS。结论 冰片、AST Ⅳ和PNS能不同程度降低脑缺血/再灌注后BBB通透性的增加,减轻脑水肿,对抗脑组织损伤,三药合用有增强效应,机制可能与协同抑制缺血后ZO-1、ZO-2、Occludin表达下调,保护BBB有关。Aim To probe the effect of borneol combined with astragalosides Ⅳ(AST Ⅳ) and Panax notoginseng saponins(PNS) on blood-brain barrier(BBB) after cerebral ischemia-reperfusion. Methods Rats with cerebral ischemia-reperfusion were admin-istered by gavage, the symptom of nerve function defect was observed,the water content of brain tissues,the permeability of BBB,and the expression of zonula cccludens 1( ZO-1),ZO-2,Occludin and Claudin-5 were detected. Results After cerebral ischemiareperfusion, the neurological deficit symptom appeared,the neurological function score and brain water content increased,and BBB was destroyed. Each drug could relieve the above pathological changes to various degrees,and the effect of borneol + AST Ⅳ + PNS was the best,which was stronger than that of single drug and AST Ⅳ + PNS. The expressions of ZO-1,ZO-2,Occludin,Claudin-5 proteins decreased after cerebral ischemia-reperfusion. All drugs inhibited the decrease of ZO-1,except AST Ⅳ,and increased Occludin expression;Borneol + AST Ⅳ + PNS also up-regulated ZO-2,and the increase in ZO-1,ZO-2,Occludin was greater than that of each drug alone and AST Ⅳ +PNS. Conclusions Borneol,AST Ⅳ and PNS can relieve the increase of BBB permeability,reduce brain edema and antagonize brain injury to various degrees after cerebral ischemia-reperfusion, which are enhanced by the combination of three drugs. The mechanism may be related to the synergistic inhibition of the down-regulation of ZO-1,ZO-2 and Occludin and the protection of BBB after cerebral ischemia.

关 键 词：冰片 黄芪甲苷 三七总皂苷 脑缺血/再灌注 血脑屏障 紧密连接蛋白 

分 类 号：R-332[医药卫生] R282.71