GM1对PC12细胞缺氧缺糖损伤中HO-1表达的影响及PI-3K/Akt通路在此过程中的作用

Effects of GM1 on Heme Oxygenase-1 Expression in PC12 Cells During Oxygen Glucose Deprivation and the Role of Phosphatidylinositol 3-kinase/Akt Pathway in the Course

目的:探讨PC12细胞缺氧缺糖损伤中,单唾液酸四己糖神经节苷脂(GM1)对血红素加氧酶(HO-1)表达的影响,并研究PI-3K/Akt通路在此过程中的作用。方法:用连二亚硫酸钠(Na2S2O4)消除培养基中的氧合并培养基质缺糖制造PC12细胞缺氧缺糖损伤(OGD)模型,用RT-PCR和Western blot方法检测不同剂量(25-100μmol/L)GM1和PI-3K抑制剂LY294002对缺氧缺糖损伤时PC12细胞HO-1mRNA及蛋白表达的影响。结果:与对照组和单纯缺氧缺糖组相比,GM1可显著上调缺氧缺糖PC12细胞的HO-1mRNA和蛋白表达,且两者呈明显的剂量依赖关系;PC12细胞经LY294002预处理后,GM1上调HO-1mRNA和蛋白表达的作用均受到抑制。结论:GM1可上调缺氧缺糖损伤时PC12细胞HO-1mRNA和蛋白表达,PI-3K/Akt通路在此过程中发挥了一定的信号转导作用。

Objective： To investigate the effects of Monosialoganglioside （GM1）on the heme oxygenase- 1 （HO-1）expression in PC12 cells during oxygen glucose deprivation （OGD）, and to study the role of phosphatidylinositol 3-kinase （PI-3K）/Akt signaling pathway in this course. Methods： An ischemical model was induced by incubation of PC12 cells with 1 mmol/L Na2 S2O4 and glucosefree medium for four hours. Cells were treated with differect dose （25-100 btmol/L）of GM1 at the same time and （or）pretreated with LY294002, an inhibitor of PI-3K during OGD. Expression of HO-1mRNA and protein was determined by RT-PCR and Western blot analysis. Results： In contrast with the control group and OGD group, GM1 could up-regulate markedly the expression of HO-1mRNA and protein during OGD. Moreover, there was characteristic dose-depended relationship between GM1 and the expression of HO-1 mRNA and protein. Pretreatment of cells with LY294002 could partially attenuated the ability of GM1 to up-regulate HO-1mRNA and protein expression. Conclusion： GM1 could up-regulate HO-1 mRNA and protein expression in PC12 cells during OGD, and PI-3K/Akt signaling pathway plays an important role in this course.