摘要
目的:观察白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)和γ-干扰素(IFN-γ)引起胰岛细胞凋亡、胰岛素分泌、Bcl-xL和Bax蛋白表达变化及其牛磺酸的影响。方法:应用体外单层培养Wistar大鼠胰岛细胞,分别检测IL-1β、TNF-α和IFN-γ对胰岛细胞凋亡细胞百分率、DNA片段、培养液中NO2-/NO3-含量及NOS活性、胰岛素分泌、Bcl-xL和Bax表达的影响,并进一步观察牛磺酸的作用。结果:IL-1β、TNF-α和IFN-γ联合可诱导胰岛细胞凋亡率明显增加,DNA明显片段化,同时NO2-/NO3-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);牛磺酸能阻断上述细胞因子的作用(P<0.01),并有一定的剂量依赖性。结论:牛磺酸能够改善IL-1β、TNF-α和IFN-γ诱导的胰岛细胞凋亡,其机制可能与抑制NOS活性从而减少NO的生成以及下调Bax/Bcl-xL比例有关。
AIM: To investigate the changes of apoptosis in isolated pancreatic islet cells, insulin secretion, expression of Bcl - xL and Bax induced by combination of IL - 1β, TNF - α and IFN - γ, and effects of taurine on them. METHODS: Isolated pancreatic islet cells from Wistar rat were incubated in monolayer in vitro. NO2^- / NO3^- production, NOS activity, insulin secretion, the protein expression of Bcl - xL and Bax, percentage of islet cell apoptosis and DNA fragmentation in pancreatic islet cells incubated with combination of IL - 1β, TNF - α and IFN - γ were measured, and the effects of taurine on the changes of them were further investigated. RESULTS : Combination of IL - 1β, TNF - α and IFN -γ induced a significant increase in percentage of pancreatic islet cell apoptosis, NO2^-/NO3^- production and NOS activity, DNA ladder appearance, a decrease in insulin content, up - regulation in the protein expression of Bax and down - regulation in the protein expression of Bcl - xL ( P 〈 0. 01 ), which were blocked by addition of taurine ( P 〈 0.01 ). These effects occurred in a dose dependent manner. CONCLUSION: Taurine attenuates 15 cell apoptosis induced by IL - 1β, TNF - α and IFN - γ. The mechanism of which may be the inhibition of NOS activity and the decrease of NO production as well as the downregulation of Bax/Bcl - xL proportion.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2007年第6期1172-1175,共4页
Chinese Journal of Pathophysiology
关键词
白细胞介素1
细胞凋亡
一氧化氮
基因表达
牛磺酸
胰岛
Interleukin - 1
Apoptosis
Nitric oxide
Gene expression
Taurine
Islets of langerhans