银杏叶总黄酮对缺氧条件下大鼠星型胶质细胞活力、细胞凋亡率及IPS-1/TRAF6信号通路的影响

Effects of Total Flavonoids in Ginkgo Folium on Astrocyte Viability,Apoptotic Rate and IPS-1/TRAF6 Signaling Pathway in Rats under Hypoxia

目的:探讨银杏叶总黄酮对缺氧条件下大鼠星型胶质细胞活力、细胞凋亡率及干扰素β启动子刺激因子1(IPS-1)/肿瘤坏死因子TNF受体相关因子6(TRAF6)信号通路的影响。方法:设立大鼠星型胶质细胞对照组(培养环境为20%O2、5%CO2、75%N2)、缺氧组(培养环境为1%O2、5%CO2、94%N2)、银杏叶总黄酮低、中、高剂量组(终浓度100,200,400μg·ml^-1)。培养结束后,测定各组细胞活力、凋亡水平、细胞周期、IPS-1、TRAF6 mRNA和蛋白水平。结果:与对照组比较,缺氧组光密度(OD)值、存活率水平显著降低(P<0.05),凋亡率、G1期水平、IPS-1、TRAF6 mRNA和蛋白水平显著升高(P<0.05);与缺氧组比较,银杏叶总黄酮各剂量组OD值、存活率水平显著升高(P<0.05),凋亡率、G1期水平、IPS-1、TRAF6 mRNA和蛋白水平显著降低(P<0.05);且各指标变化与银杏叶总黄酮浓度呈正相关(P<0.05)。结论:银杏叶总黄酮能提高缺氧条件下大鼠星型胶质细胞活力、抑制其凋亡;其机制与银杏叶总黄酮抑制星型胶质细胞IPS-1、TRAF6 mRNA和蛋白表达水平有关。

Objective:To investigate the effects of total flavonoids in Ginkgo Folium on astrocyte viability,apoptotic rate and interferonβpromoter stimulator-1(IPS-1)/tumor necrosis factor receptor associated factor 6(TRAF6)signaling pathway in rats under hypoxia.Methods:Rat astrocyte control group(20%O2,5%CO2,75%N2),hypoxia group(1%O2,5%CO2,94%N2)and low,medium and high(final concentration 100,200 and 400μg·ml-1)dose groups of total flavonoids in Ginkgo Folium were established.After the culture,the cell viability,apoptotic level,cell cycle,IPS-1,TRAF6 mRNA and protein levels were measured.Results:Compared with those of the control group,the OD value and survival rate of the hypoxic group significantly decreased(P<0.05),and the apoptotic rate,G1 level,IPS-1,TRAF6 mRNA and protein levels significantly increased(P<0.05);compared with those of the hypoxic group,the OD value and survival rate of total flavonoids in Ginkgo Folium groups were significantly increased(P<0.05),and the apoptotic rate,G1 level,IPS-1,TRAF6 mRNA and protein levels significantly decreased(P<0.05);the change of each index was positively correlated with the concentration of total flavonoids in Ginkgo Folium(P<0.05).Conclusion:Total flavonoids in Ginkgo Folium can increase the viability and inhibit apoptosis of astrocytes in rats under hypoxia.The mechanism is related to the inhibition of IPS-1,TRAF6 mRNA and protein expressions of total astrocytes by Ginkgo biloba.