摘要
目的:探讨二甲双胍对干扰素(interferon,IFN)-γ诱导的人卵巢颗粒细胞KGN功能损伤的效应及可能机制。方法:采用CCK-8法检测不同浓度二甲双胍单独及与IFN-γ共处理对KGN细胞活力的影响,并观察细胞生长状态的变化;流式细胞术检测不同处理对KGN细胞凋亡及周期的影响;q-PCR法检测细胞周期蛋白依赖性激酶抑制剂1A(cyclin dependent kinase inhibitor 1A,CDKN1A)mRNA的表达。结果:IFN-γ可抑制KGN细胞活力、阻滞细胞从G0-G1期进入S期,并促进凋亡(P <0.05);二甲双胍单独处理几乎不影响KGN细胞功能;但二甲双胍与IFN-γ共同作用可提高损伤的KGN细胞活力,缓解IFN-γ引起的细胞凋亡及周期阻滞,并抑制细胞周期负性调节蛋白CDKN1A表达的异常上调。结论:二甲双胍可减轻IFN-γ诱导的KGN细胞功能损伤,并且可能是通过下调细胞周期负性调节蛋白CDKN1A的异常表达发挥保护作用。
Objective:This study aims to investigate the effects and potential mechanisms of metformin on the inflammatory cytokine interferon(IFN)-γ induced cell damage in human ovarian granulosa cells KGN. Methods:The effects of metformin alone and with IFN-γ on the viability of KGN cells were detected using CCK-8 kit,and the cell growth status of KGN cells were observed under microscope. The apoptotic cells and the cell cycle in KGN cells were analyzed using flow cytometry. The mRNA expression levels of cyclin dependent kinase inhibitor 1 A(CDKN1 A),a gene related to cell cycle regulation,were analyzed using q-PCR. Results:IFN-γtreatment inhibited the vitality of KGN cells through blocking these cells from G0-G1 phase to S phase and promoting into apoptosis.Although metformin treatment alone had no obvious effects on the KGN cells,it alleviated the apoptosis in KGN cells and reversed the cell cycle which induced by IFN-γ. Moreover,metformin significantly inhibited the expression levels of CDKN1 A in IFN-γ treated KGN cells. Conclusion:Metformin had a protective role on the IFN-γ induced cell injury in KGN cells by down-regulating the abnormal expression of the negative cell cycle regulator CDKN1 A in these cells.
作者
姚雪
刘烁
俞宛君
陶泽华
蒋雅斓
陈少聃
冉银宏
夏圣
YAO Xue;LIU Shuo;YU Wanjun;TAO Zehua;JIANG Yalan;CHEN Shaodan;RAN Yinhong;XIA Sheng(Department of Immunology,School of Medicine,Jiangsu University,Zhenjiang 212013,China)
出处
《南京医科大学学报(自然科学版)》
CAS
CSCD
北大核心
2021年第8期1135-1140,共6页
Journal of Nanjing Medical University(Natural Sciences)
基金
国家自然科学基金资助(81871234)。