丹酚酸B、人参皂苷Rg1及三七皂苷R1对氧糖剥夺/复氧复糖损伤星形胶质细胞的保护作用  

The protective effects of salvianolic acid B,ginsenoside Rg1 and notoginsenoside R1 on oxygen-glucose deprivation/reoxygenation and reoxygenation of astrocytes

作　　者：杨娟 曹玉爽 徐耀 杜鑫苑 张彤 郭莉琛 袁庆[1] 柴丽娟[1] 胡利民[1] YANG Juan;CAO Yu-shuang;XU Yao;DU Xin-yuan;ZHANG Tong;GUO Li-chen;YUAN Qing;CHAI Li-juan;HU Li-min(Institute of Traditional Chinese Medicine,Tianjin University of TCM,Tianjin Key Laboratory of Chinese Medicine Pharmacology,Key Laboratory of Pharmacology of TCM Formulae,Ministy of Education,Tianjin 301600,China)

机构地区：[1]天津中医药大学中医药研究院、天津市中药药理学重点实验室、方剂学教育部重点实验室,天津301600

出　　处：《中国药理学通报》2022年第10期1466-1472,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81573644)。

摘　　要：目的探讨丹酚酸B(salvianolate acid B,Sal B)、人参皂苷Rg1(ginsenoside Rg1,Rg1)及三七皂苷R1(notoginsenoside R1,R1)对氧糖剥夺/复氧复糖(OGD/R)损伤大鼠星形胶质细胞保护作用及其机制的影响。方法培养并鉴定原代大鼠星形胶质细胞,建立OGD/R损伤模型,分为对照组、模型组、Sal B、Rg1、R1给药组(10μmol·L^(-1))。CCK-8测定细胞活力;流式细胞术测定线粒体膜电位、ROS释放量和钙离子浓度;RT-PCR测定IGF1α、BDNF、NGF神经营养因子mRNA表达水平;免疫印迹法测定PI3K、AKT、STAT3蛋白磷酸化表达水平。结果OGD/R组细胞活力显著降低,ROS释放量及钙离子浓度增加,线粒体膜电位降低,p-STAT3,p-PI3K,p-AKT表达下降,Sal B、Rg1、R1显著提高受损细胞活力,不同程度的调节ROS释放量、钙离子浓度、线粒体膜电位,Sal B及Rg1增加p-STAT3,p-AKT的表达;OGD/R组BDNF、NGF mRNA表达明显降低,Sal B、Rg1、R1均可显著升高受损细胞BDNF mRNA的表达;Rg1可提高NGF mRNA表达;Sal B升高IGF1αmRNA表达。结论Sal B、Rg1、R1通过调节PI3K/AKT、STAT3信号通路降低OGD/R损伤后星形胶质细胞氧化应激反应,降低细胞内钙离子超载发挥星形胶质细胞保护作用,增加星形胶质细胞神经营养因子的释放量,可能进一步发挥神经元保护作用。Aim To investigate the protective effects of salvianolate acid B(Sal B),ginsenoside Rg1(Rg1)and notoginsenoside R1(R1)on astrocytes after oxy-glucose deprivation/reoxygenation(OGD/R)injury and the underlying mechanism.Methods Primary rat astrocytes were cultured and identified to establish OGD/R injury model.The cells were divided into control group,model group and Sal B,Rg1 and R1 treatment groups(10μmol·L^(-1)).The CCK-8 cell proliferation-toxicity test kit was used to detect the cell viability of astrocytes,and flow cytometry to detect mitochondrial membrane potential,ROS release and intracellular calcium concentration.RT-PCR was employed to detect the mRNA expression of BDNF,NGF,IGF1αin astrocytes.Western blot was used to detect the phosphorylation of PI3K,AKT and STAT3 protein in astrocytes.Results OGD/R significantly decreased cell viability.ROS release and intracellular calcium ion concentration of astrocytes,mitochondrial membrane potential and p-STAT3,p-PI3K,p-AKT expression decreased in OGD/R group.Sal B,Rg1 and R1 significantly increased the viability of damaged cells,and regulated ROS release,calcium ion concentration and mitochondrial membrane potential to varying degrees.Sal B and Rg1 increased the expression of p-STAT3 and p-AKT.The expression of BDNF and NGF mRNA in OGD/R group significantly decreased,and Sal B,Rg1 and R1 could significantly increase the expression of BDNF mRNA in damaged cells.Rg1 could increase NGF mRNA expression.Sal B increased the expression of IGF1αmRNA.Conclusions Sal B,Rg1,and R1 reduce the oxidative stress response of astrocytes after OGD/R injury by regulating the PI3K/AKT and STAT3 signaling pathway,reduce intracellular calcium overload,and play a protective role in astrocytes,increase the release of astrocyte neurotrophic factor,which may further play a protective role in neurons.

关 键 词：丹酚酸B 人参皂苷RG1 三七皂苷R1 星形胶质细胞 氧糖剥夺/复氧复糖 氧化损伤 神经营养因子 

分 类 号：R-332[医药卫生] R284.1R322.81R329.24R852.15