黄芪甲苷对脑缺血-再灌注损伤大鼠神经的影响及作用机制  

Effect and mechanism of astragalosideⅣon cerebral ischemia-reperfusion injury in rats

作　　者：李广从 靳春晓 刘宁 LI Guangcong;JIN Chunxiao;LIU Ning(Department of Neurology,Cangzhou Central Hospital,Cangzhou 061000,China;Department of Internal Medicine,Gequan Branch Hospital of Jizhong Energy Xingtai Mining Group Limited Company,Hengshui 053000,China;Department of Neurology,Xingtai People’s Hospital,Xingtai 054000,China)

机构地区：[1]沧州市中心医院神经内科,沧州061000 [2]冀中能源邢台矿业集团有限责任公司葛泉分公司医院内科,衡水053000 [3]邢台市人民医院神经内科,邢台054000

出　　处：《西北药学杂志》2024年第3期46-51,共6页Northwest Pharmaceutical Journal

基　　金：河北省2021年度医学科学研究课题计划项目(编号:20211810)。

摘　　要：目的探讨黄芪甲苷(astragalolosideⅣ,AS-Ⅳ)对脑缺血-再灌注(cerebral ischemia-reperfusion injury,CI-RI)大鼠脑损伤的影响及可能的作用机制。方法选取65只大鼠采用大脑中动脉阻塞线栓法(middle cerebral artery occlusion,MCAO)建立CI-RI模型,将造模成功大鼠随机分为模型组、AS-Ⅳ低剂量组、AS-Ⅳ中剂量组和AS-Ⅳ高剂量组,另设对照组,各12只。AS-Ⅳ低剂量组、AS-Ⅳ中剂量组和AS-Ⅳ高剂量组分别灌胃20、40、80 mg·kg^(-1) AS-Ⅳ混悬液(蒸馏水配制),对照组及模型组给予等量蒸馏水。评价大鼠神经功能缺损情况;用酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测各组大鼠血清肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)、丙二醛(malondialdehyde,MDA)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)和超氧化物岐化酶(superoxide dismutase,SOD)水平;HE染色观察各组大鼠脑组织病理变化;用实时荧光定量聚合酶链反应(real-time quantitative polymerase chain reaction,RT-qPCR)和蛋白印迹法(Western blotting)分别检测大鼠脑组织中过氧化物酶体增殖物受体γ共激活因子1α(peroxisome proliferator receptorγcoactivator,PGC-1α)、核因子E2相关因子2(nuclear factor E2 related factor 2,Nrf2)mRNA和蛋白的表达情况。结果与模型组比较,AS-Ⅳ低、中、高剂量组大鼠各时间神经功能学Garcia JH评分、GSH-Px、SOD、PGC-1α、Nrf2 mRNA和蛋白表达水平均升高,TNF-α、IL-1β、IL-6、MDA水平均降低(P<0.05)。与AS-Ⅳ低剂量组比较,AS-Ⅳ中剂量、AS-Ⅳ高剂量组诸项指数水平的改变更明显,且AS-Ⅳ高剂量组的变化更显著(P<0.05)。结论AS-Ⅳ能够改善MCAO大鼠神经功能损伤,降低氧化应激水平,改善神经炎症,可能是通过激活PGC-1α/Nrf2信号通路发挥作用的。Objective To investigate the effect of astragalosideⅣ(AS-Ⅳ)on brain injury in cerebral ischemia-reperfusion(CI-RI)rats and its possible mechanism.Methods 65 rats were selected to establish cerebral ischemia-reperfusion model by middle cerebral artery occlusion thread occlusion(MCAO).The successful rats were randomly divided into model group,low,medium and high doses of AS-Ⅳgroup,and another control group,with 12 rats in each group.The low,medium and high doses of AS-Ⅳgroups were gavaged with 20,40 and 80 mg·kg^(-1)AS-Ⅳsuspension(prepared with distilled water),respectively,and the control and model group were given the same amount of distilled water.The neurological deficit of rats was evaluated.The levels of serum tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),malondialdehyde(MDA),glutathione peroxidase(GSH-Px)and superoxide dismutase(SOD)were detected by enzyme linked immunosorbent assay(ELISA).The pathological changes of rat hippocampal were observed by HE staining.The mRNA and protein expressions of peroxisome proliferator receptorγcoactivator 1α(PGC-1α)and nuclear factor E2 related factor 2(Nrf2)in rats hippocampus were detected by real-time quantitative polymerase chain reaction(RT-qPCR)and western blotting.Results Compared with the model group,the levels of neurological Garcia JH score at each time,GSH-Px,SOD,PGC-1 and Nrf2 mRNA and protein expression were increased,the levels of TNF-α,IL-1β,IL-6 and MDA were decreased in low,medium and high doses of AS-Ⅳgroups(P<0.05).Compared with low dose of AS-Ⅳgroup,the index levels medium and high doses of AS-Ⅳgroups changed significantly,especially in high doses of AS-Ⅳgroup(P<0.05).Conclusion AS-Ⅳcan improve the neurological injury,reduce the level of oxidative stress and improve neuroinflammation in MCAO rats,possibly by activating PGC-1α/Nrf2 signaling pathway.

关 键 词：黄芪甲苷 脑缺血-再灌注损伤 神经保护 过氧化物酶体增殖物受体γ共激活因子1α 核因子E2相关因子2 

分 类 号：R965[医药卫生—药理学]