【摘要】 目的:观察白细胞介素-1β(IL-1β)、肿瘤坏死因子(TNF)和γ-干扰素(IFN-γ)引起胰岛细胞凋亡、胰岛素分泌、bcl-xl和bax蛋白表达的变化。方法:应用体外单层培养的3￣5天的W istar大鼠胰岛细胞,分别检测IL-1β、TNF和IFN-γ对胰岛细胞凋亡细胞百分率、以及培养液中基础和高糖刺激下胰岛素分泌量、NO含量、NOS活性、bcl-xl和bax蛋白表达以及DNA片段的影响。结果:IL-1β、TNF和IFN-γ联合可诱导胰岛细胞凋亡率明显增加及DNA明显片段化,同时NO含量和NOS活性亦明显升高,胰岛素分泌明显降低,bcl-xl表达下降和bax表达增强(P<0.01),且有时间和剂量依赖性。结论:细胞因子能诱导胰岛细胞凋亡,其机制可能与提高NOS活性从而增加NO的生成以及上调bax/bcl-xl比例有关。更多还原

【Abstract】 Objective: To investigate the apoptosis of isolated pancreatic islet cells and insulin secretion induced by combination of IL-1β,TNF and IFN-γ,and to investigate the mechanism of the change.Methods: Isolated pancreatic islet cells from Wistar rat were incubated in monolayer in vitro.NO production,NOS activity,insulin secretion,the protein expression of bcl-xl and bax,apoptotic rate of islet cells and DNA fragmentation in pancreatic islet cells incubated with combination of IL-1β,TNF and IFN-γ were measured.Results: Combination of IL-1β,TNF and IFN-γ induced a significant increase in apoptotic percentage of pancreatic islet cells,NO production and NOS activity,as well as DNA ladder appearance,while a decrease in insulin content.Up-regulation of the protein expression of bax and down-regulation of the protein expression of bcl-xl were also induced(P<0.01).These effects occurred in a time and dose dependent manner.Conclusion: The cytokines can induce β cell apoptosis,the mechanism of which may be the activation of NOS and the increase of NO production and the upregulation of bax/bcl-xl proportion.更多还原