黄芪甲苷和三七的三种有效成分配伍对小鼠脑缺血/再灌注后氧化应激和Nrf2/HO-1途径的影响  

Effects of combinations of astragaloside Ⅳ and three active components in notoginseng on oxidative stress and Nrf2 /HO-1 pathway after cerebral ischemic-reperfusion in mice

作　　者：黄小平[1] 邓常清[2] 邱咏园[3] 王蓓[3] 唐映红[3] 曾嵘[3] 

机构地区：[1]湖南中医药大学医学院,湖南长沙410208 [2]湖南中医药大学中西医结合学院,湖南长沙410208 [3]湖南中医药大学药学院,湖南长沙410208

出　　处：《中国药理学通报》2013年第11期1596-1601,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81102557);教育部高等学校博士学科点专项科研基金资助项目(No20104323110001);湖南省高校创新平台开放基金资助项目(No 11K050);湖南省教育厅项目(No 11C0963);湖南省高校科技创新团队支持计划项目

摘　　要：目的研究黄芪的主要有效成分黄芪甲苷分别与三七的有效成分人参皂苷Rg1、人参皂苷Rb1、三七皂苷R1配伍对小鼠脑缺血/再灌注后氧化应激和核转录因子E2相关因子2(nuclear factor-erythroid 2 related factor 2,Nrf2)/血红素加氧酶(heme oxygenase,HO)-1途径的影响。方法C57BL/6小鼠随机分组,连续给药3 d,末次给药1 h后,结扎双侧颈总动脉造成脑缺血20 min,再灌注24 h。测定脑组织丙二醛(malonyldialdehyde,MDA)、一氧化氮(nitric oxide,NO)、超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽(glutathione,GSH),HO-1mRNA表达,脑组织胞核、胞质Nrf2和全细胞HO-1蛋白表达。结果①脑缺血/再灌注后,脑组织MDA、NO含量明显升高,SOD活性和GSH含量明显降低。黄芪甲苷可降低脑组织MDA、NO含量,人参皂苷Rg1能降低脑组织NO含量。黄芪甲苷+人参皂苷Rg1、黄芪甲苷+人参皂苷Rb1和黄芪甲苷+三七皂苷R1均能明显降低脑组织MDA和NO含量,且黄芪甲苷与人参皂苷Rb1、三七皂苷R1配伍的效应大于人参皂苷Rb1单用和三七皂苷R1单用。②脑缺血/再灌注后,脑组织胞核和胞质中Nrf2蛋白含量及核转位率升高,同时HO-1mRNA和蛋白表达增强。各给药组能不同程度地降低胞质Nrf2蛋白含量,升高胞核Nrf2含量,使Nrf2核转位率升高,且黄芪甲苷+人参皂苷Rg1、黄芪甲苷+人参皂苷Rb1、黄芪甲苷+三七皂苷R1的作用强于各有效成分单用。黄芪甲苷、人参皂苷Rg1、黄芪甲苷+人参皂苷Rg1、黄芪甲苷+人参皂苷Rb1、黄芪甲苷+三七皂苷R1可使脑组织HO-1mRNA和蛋白表达明显增加,黄芪甲苷+人参皂苷Rg1、黄芪甲苷+人参皂苷Rb1、黄芪甲苷+三七皂苷R1脑组织HO-1mRNA和蛋白的增加明显高于各有效成分单用。且黄芪甲苷+人参皂苷Rg1升高胞核Nrf2蛋白、提高Nrf2核转位率的作用强于黄芪甲苷+人参皂苷Rb1,增加HO-1基因和蛋白表达的作用强于黄芪甲苷+人参皂苷Rb1和黄芪甲苷+三七�Aim To investigate the effects of the combinations of Astragaloside iV （the effective component of Astragalus ） and Ginscnoside Rgl, Ginscnoside Rbl, Notoginsenoside R1 （the effective components of Panax notoginseng） on oxidative stress and nuclear factor-erythroid 2 related factor 2 （Nrf2）/heme oxygenase （HO） -1 pathway after cerebral ischemic-reperfusion in mice. Methods C57BL/6 mice were randomly grouped, treated for 3 days, and 1 h after the last ad- ministration, cerebral ischemia-reperfusion injury was established by bilateral common carotid artery ligation for 20 rain followed by reperfusion for 24 h. Malondialdehyde （ MDA）, nitric oxide （ NO）, superoxide dismutase （ SOD）, glutathione （ GSH）, HO-1 mRNA expression in tissues and the expressions of Nrf2 in cytoplasm and nucleus, HO-1 in whole cell were determined. Results 1. After cerebral ischemic reperfusion for 24 h, the contents of MDA, NO were increased, SOD activity and GSH level were decreased as well. Astragaloside Ⅳ significantly inhibited the increase of MDA, NO, and Ginsenoside Rgl obviously reduced NO content. Astragaloside Ⅳ ＋ Ginsenoside Rgl, Astragaloside Ⅳ ＋ Ginsenoside Rbl and Astragaloside Ⅳ ＋ Notoginsenoside R1 obviously all reduced the contents of MDA and NO, and the effects of Astragaloside Ⅳ ＋ Ginsenoside Rbl and Astragaloside Ⅳ ＋ Notoginsenoside R1 were better than those of Ginsen- oside Rbl, Notoginsenoside R1 alone. 2. After cerebral ischemic reperfusion for 24 h, Nrf2 protein content was increased in cytoplasm and nucleus, nuclear translocation rate was raised, at the same time, HO- 1mRNA and HO-1 protein expression in brain tissues were significantly up-regulated. In different Nrf2 protein content was toplasm and significantly significantly decreased in cyincreased in nucleus, nuclear translocation rate was raised in treatment groups, and the effects of Astragaloside Ⅳ ＋ Ginsenoside Rgl, Astragaloside Ⅳ ＋ Ginsenoside Rbl and Astragaloside Ⅳ ＋ Notoginsenoside R1 were

关 键 词：脑缺血 再灌注损伤 中药有效成分 配伍 黄芪甲苷 人参皂苷Rg1 人参皂苷Rb1 三七皂苷R1 氧化应激 核转录因子E2相关因子2 血红素加氧酶-1 

分 类 号：R-332[医药卫生] R284.1