人参皂苷Rg1对小鼠脑缺血再灌注后脑组织损伤及Nrf2/HO-1途径的影响  

Effects of ginsenoside Rg1 of Panax notoginseng on brain tissue injury and Nrf2/HO-1 signal pathway after cerebral ischemia/reperfusion in mice

作　　者：吴露[1] 黄小平[2] 邓常清[2] 严杰[2] 张秋雁[2] 

机构地区：[1]湖南中医药大学附属第二中西医结合医院心血管科,湖南浏阳410300 [2]湖南中医药大学,湖南长沙410208

出　　处：《中国病理生理杂志》2013年第11期2066-2071,共6页Chinese Journal of Pathophysiology

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(No.20104323110001);湖南省高校创新平台开放基金资助项目(No.11K050);湖南省中医药管理局重点项目(No.201301);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:观察人参皂苷Rg1对小鼠脑缺血再灌注后脑组织损伤的影响,并从核因子E2相关因子2(Nrf2)/血红素加氧酶1(HO-1)信号通路研究其作用机制。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。以具有抗氧化应激损伤作用、治疗缺血性脑血管病有效的药物依达拉奉作为阳性对照药。取脑组织行海马CA1区神经细胞病理学测定,RT-PCR法测定Nrf2和HO-1mRNA表达,Western bloting测定脑组织胞核、胞浆Nrf2和全细胞HO-1蛋白含量。结果:(1)缺血再灌注24 h后,神经细胞出现病理性损伤,细胞存活率显著降低。人参皂苷Rg1和依达拉奉可使神经细胞损伤明显减轻,细胞存活率显著升高。(2)脑缺血再灌注24 h,脑组织Nrf2 mRNA和HO-1 mRNA表达增强,同时脑组织胞核和胞浆中Nrf2蛋白含量增加,核转位率升高,HO-1蛋白表达增强。人参皂苷Rg1和依达拉奉均能降低脑组织胞浆Nrf2蛋白含量,升高胞核Nrf2含量,使Nrf2核转位率升高,并使脑组织HO-1 mRNA和蛋白表达显著增加。依达拉奉的作用强于人参皂苷Rg1,但两药对脑组织Nrf2 mRNA表达无显著影响。结论:人参皂苷Rg1具有抗脑缺血再灌注损伤的作用,其机制可能与激活Nrf2/HO-1信号途径、促进Nrf2合成和核转位、从而促进下游抗氧化蛋白HO-1的表达有关。AIM： To observe the effects of ginsenoside Rgl of Panax notoginseng on brain tissue injury after mouse cerebral ischemia/reperfusion （I/R）, and to explore the mechanisms involving nuclear factor E2-related factor 2 （Nrf2）/heme oxygenase 1 （ HO-1 ） signal pathway. METHODS： C57BL/6 mice were randomly divided into sham group, cerebral I/R group, ginsenoside Rgl ＋ cerebral I/R group and edaravone ＋ cerebral I/R group. Ginsenoside Rgl was successively administered for 3 d. One hour after final administration, bilateral common carotid arteries were ligated to induce brain tissue injury for 20 min, and then reperfusion for 24 h. Edaravone, a drug for anti-oxidative stress injury in the treatment of ischemic cerebro-vascular disease, was used as a positive control. The brain tissues were obtained to determine the neural cellular pathology in hippocampal CA1 region. The mRNA expression of Nrf2 and HO-1 was detected by RT-PCR. The protein levels of Nr/2 in the nucleus and cytoplasm and HO-1 in the whole cells in the brain tissues were measured by Western blotting. RESULTS ： After ischemia/reperfusion for 24 h, the pathological injury in the neural cells was obvious, and the cell survival rate decreased. Ginsenoside Rgl and edaravone attenuated the neural cell injury, and significantly increased the cell survival rate. After ischemia/reperfusion for 24 h, the mRNA expression of Nrf2 and HO-1 significantly increased in the brain tissues. The protein levels of Nrf2 in the nucleus and cytoplasm in the brain tissues were increased, thenuclear translocaition rate and tile protein expression of HO-I also increased. Ginsenoside Rgl and edaravone both decreased the protein levels of Nrf2 in the cytoplasm of the brain tissues, increased that in the nucleus, and also inereased Nrf2 nuclear transloeation rate and the protein expression of HO-1. The effect of edaravone was higher than that of ginsenoside Rgl, but they had no significant effect on the mRNA expression of Nrf2 in the brain tissues. CONCLUSION： Gins

关 键 词：脑缺血 再灌注损伤 人参皂苷RG1 氧化性应激 核因子E2相关因子2 血红素加氧酶1 

分 类 号：R285.5[医药卫生—中药学]