尼克酰胺对白介素-1β损伤的离体大鼠胰岛细胞的保护作用

Protective effects of nicotinamide against interleukin-1β-induced destruction of isolated rat pancreatic islets of Langerhans

目的 观察尼克酰胺（ＮＡ）对白细胞介素－１β（ＩＬ－１β）诱导的胰岛细胞损害的保护作用。方法应用体外单层培养的大鼠胰岛细胞，分别检测ＩＬ－１β，ＮＡ（１０，２０ｍｍｏｌ／Ｌ）及其联合对胰岛细胞亚硝酸盐生成，胰岛素分泌以及胞内ＤＮＡ，胰岛素含量和细胞活性的影响。结果 由ＩＬ－１β诱导的胰岛细胞亚硝酸盐生成量显著增加，同时胰岛素基础分泌以及葡萄糖刺激的胰岛素释放均明显减少；胰岛细胞内 ＤＮＡ，胰岛素含量及细胞活性（ＭＴＴ值）均显著下降（Ｐ均＜０．００１）；较高浓度及其的 ＮＡ（２０ ｍｍｏｌ／Ｌ）能阻断这些抑制作用（Ｐ均＜ ０．００１）；而较低浓度的 ＮＡ（１０ ｍｍｏｌ／Ｌ）虽不能阻断 ＩＬ－１β诱导的 ＮＯ生成对葡萄糖刺激的胰岛素释放的抑制作用，但对 ＩＬ－１β介导的其它抑制作用仍呈现保护性效应（Ｐ均＜ ０．００１）。结论 一氧化氮（ＮＯ）虽然参与ＩＬ－１β诱导的胰岛细胞的损害过程，但可能不是唯一的效应分子。ＮＡ可能通过包括抑制ＮＯ生成等多方面机制，实现对ＩＬ－１β诱导的胰岛细胞损害的保护作用。

The effects of nicotinamide (NA)'on interleukin-ip-induced destruction of isolated rat pancreatic islets of Langerhans were observed. Method Isolated pancreatic islet cells from SD rat were cultured in monolayer in vitro. Nitrite production, insulin release, islet cell DNA and insulin content, and cell activity (MTT assay ) in rat pancreatic islet cells incubated with IL-1β or/and NA (10,20 mmol/L),were measured. Results IL-lp induced a significant increase in nitrite production, inhibited the medium insulin accumulation and the glucose-stimulated insulin .release, and decreased islet cell DNA insulin content and MTT(P< 0. 001 ) . The inhibitory activities were blocked by NA in a higher dose (20 mmol/ L) (P< 0.001) while in a lover dose. NA (10 mmol/L) prevented the IL-lp-induced cy-totoxic effects without affecting nitrite production and the glucose-stimulated insulin release. Conclusion IL-lp-induced nitric oxide (NO) production alone is insufficient to account for the IL-lj3-mediated islet (3-cell destruction. Mechanisms of other action of the IL-1(3 may be involved. There may be a variety of mechanisms the protective effects of NA against cytotoxic action of IL-1(3, including inhibition of NO Production, which may be related to exposure concentration of NA.