中国药理学通报2017，Vol.33Issue(2)：235-242,243,9.DOI:10.3969/j.issn.1001-1978.2017.02.018
黄芪甲苷与人参皂苷 Rg1配伍抗 PC12细胞氧糖剥夺／复糖复氧后自噬性损伤相互作用的研究
Interaction of Astragaloside Ⅳcombined with Ginsenoside Rg1 against autophagy injury of PC12 cells induced by oxygen glucose deprivation/reoxygenation
摘要
Abstract
Aim To probe the effect and the interac-tion of Astragaloside Ⅳ and Ginsenoside Rg1 on auto-phagy injury of PC1 2 cells induced by oxygen glucose deprivation /reoxygenation(OGD /R).Methods Auto-phagy injury model of PC1 2 cells induced by OGD /R was established,Astragaloside Ⅳ and Ginsenoside Rg1 were divided into different dosages to interfere PC1 2 cells,the autophagosome was detected to assess the effect of drugs on autophagy injury with confocal micro-sopy,and median inhibitory concentration (IC50 )of Astragaloside Ⅳ and Ginsenoside Rg1 was calculated. Taking IC50 of Astragaloside Ⅳ and Ginsenoside Rg1 as 1 unit,the combinations of different ratios of Astragalo-side Ⅳ and Ginsenoside Rg1 (1 ∶2,1 ∶1 ,2 ∶1 ) were set up according to Isobologram method, the effect of the drugs against cells autophagy injury was determined and IC50 of different ratio combinations was acquired,then the nature of interaction was analysed that Astragaloside Ⅳ combined with Ginsenoside Rg1 inhibited autophagy through Isobologram analysis, 95% confidence and interaction index γ.On this ba-sis,using the combination of IC50 that Astragaloside Ⅳcombined with Ginsenoside Rg1 exerting synergy effect to assess the effect on cell injury and autophagy via cell survival rate,lactate dehydrogenase (LDH) leakage rate,the number of autophagosome and the expression of p62 protein.Results IC50 and 95% confidence that Astragaloside Ⅳ and Ginsenoside Rg1 inhibited autophagy was (27.22 ±0.61 4)mg · L -1 [25.96, 29.03],(1 3.68 ±1 .334)mg·L -1 [1 0.27,1 6.95], respectively.Astragaloside Ⅳ combined with Ginsen-oside Rg1 obtained a synergitic effect under 1 ∶1 ratio while presented the antagonism under 1 ∶2 or 2 ∶1 . The verification results showed that Astragaloside Ⅳ, Ginsenoside Rg1 and the combination could enhance cell survival rate,relieve LDH leakage,reduce the numbers of autophagosome and LC3-Ⅱ,and increase the expression of p62;the effects of the combination were better than those of drugs alone.Furthermore, factorial analysis manifested that Astragalus IC50 com-bined Ginsenoside Rg1 IC50 with 1 ∶1 ratio presented the interactions on cell survival,LDH leakage and au-tophagosome formation.Conclusions After OGD 2 h followed by reoxygenation 24 h,PC1 2 cells suffer ex-cessive autophagy and damage,which are prevented by Astragaloside Ⅳ combined Ginsenoside Rg1 with 1 ∶1 ratio.Moreover,the combination plays the synergitic inhibition on autophagy injury.关键词
黄芪甲苷/人参皂苷 Rg1/配伍/PC1 2 细胞/细胞自噬/Isobologram 分析/相互作用Key words
Astragaloside Ⅳ/Ginsenoside Rg1/com-bination/PC1 2 cells/autophagy/Isobologram analy-sis/interaction分类
医药卫生引用本文复制引用
丁煌,李静娴,唐标,刘晓丹,李玲,唐映红,邓常清,黄小平..黄芪甲苷与人参皂苷 Rg1配伍抗 PC12细胞氧糖剥夺／复糖复氧后自噬性损伤相互作用的研究[J].中国药理学通报,2017,33(2):235-242,243,9.基金项目
国家自然科学基金资助项目（No 81573875，81503385）；湖南省高校创新平台开放基金资助项目（No 14K068）；湖南省科技厅资助项目（No 2014SK3001）；湖南省研究生科研创新项目（No CX2016B372）；湖南省教育厅资助项目（No 14C0844）；湖南省中医药管理局重点项目（No 201301，201508）；中医内科重大疾病防治及成果转化省部共建教育部重点实验室开放课题（No ZYNK201405）；“中西医结合防治心脑血管疾病的相关基础研究”湖南省高校科技创新团队；“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 （）
