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

im To investigate the effects of the combinations between Astragaloside Ⅳ (the effective component of Astragalus) and Ginsenoside Rg1, Ginsenoside Rb1, 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, at 1 h after the last administration, cerebral ischemia-reperfusion injury was established by bilateral common carotid artery ligation for 20 min followed by reperfusion for 24 h. To detect malondialdehyde (MDA)、nitric oxide (NO)、superoxide dismutase (SOD)、glutathione (GSH), HO-1mRNA expression in tissues and the expressions of Nrf2 in cytoplasm and nucleus、HO-1 in whole cell. Results 1. After cerebral ischemic reperfusion for 24 h, the contents of MDA、NO significantly were increased, SOD activity and GSH level were decreased. Astragaloside Ⅳ significantly inhibited the increase of MDA, NO, Ginsenoside Rg1 obviously reduced NO content. Astragaloside Ⅳ+Ginsenoside Rg1, Astragaloside Ⅳ+Ginsenoside Rb1 and Astragaloside Ⅳ+Notoginsenoside R1 all reduced obviously the contents of MDA and NO, and the effects in Astragaloside Ⅳ+Ginsenoside Rb1 and Astragaloside Ⅳ+Notoginsenoside R1 were better than those in Ginsenoside Rb1, 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 degree, Nrf2 protein content was significantly decreased in cytoplasm and significantly increased in nucleus, nuclear translocation rate was raised in treatment groups, and the effects in Astragaloside Ⅳ+Ginsenoside Rg1, Astragaloside Ⅳ+Ginsenoside Rb1 and Astragaloside Ⅳ+Notoginsenoside R1 were better than those in the active components alone. Astragaloside Ⅳ, Ginsenoside Rg1, Astragaloside Ⅳ+Ginsenoside Rg1, Astragaloside Ⅳ+Ginsenoside Rb1 and Astragaloside Ⅳ+Notoginsenoside R1 could obviously increase HO-1 mRNA and HO-1 protein, and the effects in Astragaloside Ⅳ+Ginsenoside Rg1, Astragaloside Ⅳ+Ginsenoside Rb1 and Astragaloside Ⅳ+Notoginsenoside R1 were better than those in the active components alone. Furthermore, the elevatory effects of Nrf2 in nucleus, nuclear translocation rate in Astragaloside Ⅳ+Ginsenoside Rg1 were stronger than those in Astragaloside Ⅳ+Ginsenoside Rb1, the elevatory effects of HO-1 mRNA and HO-1 protein were stronger than those in Astragaloside Ⅳ+Ginsenoside Rb1 and Astragaloside Ⅳ+Notoginsenoside R1. Conclusion Astragaloside Ⅳ respectively combined with three active components of Panax notoginseng strengthened the antagonism effects on oxidative stress injury after cerebral ischemic-reperfusion, the mechanism underlying might be associated with activating Nrf2/HO-1 signal transduction pathway, promoting the synthesis and nuclear translocation of Nrf2, then advancing the expression of antioxidant gene in the downstream such as HO-1, which were more obvious in Astragaloside Ⅳ+Ginsenoside Rg1.