氨基胍对白细胞介素－1β所致胰岛损伤的保护作用

Protective effects of aminoguanidine against interleukin-1β induced damage to rat pancreatic islets of Langerhans

白细胞介素－１β（ＩＬ－１β）对胰岛β细胞具有细胞毒效应。本实验采用离体培养的新生大鼠胰岛，观察ＩＬ－１β对胰岛素分泌、ＤＮＡ合成和一氧化氮（ＮＯ）生成的影响及氨基胍对胰岛功能的保护作用。结果：①ＩＬ－１β（１０、２０、４０Ｕ／ｍｌ）孵育胰岛２４小时后，可抑制急性高浓度葡萄糖刺激的胰岛素分泌和胰岛３Ｈ－ＴｄＲ掺入量，具有明显的剂量依赖性，且其抑制程度与亚硝酸盐的生成量密切相关。②氨基胍（０．１、０．２、０．４ｍｍｏｌ／Ｌ）抑制亚硝酸盐的生成，同时减轻或完全阻断ＩＬ－１β对胰岛素分泌和３Ｈ－ＴｄＲ掺入的影响，呈剂量依赖性。实验结果表明：ＩＬ－１β对胰岛β细胞的细胞毒效应由ＮＯ介导，氨基胍通过抑制ＮＯ的合成阻断了ＩＬ－１β的胰岛损伤效应。

The effects of interleukin-1β(IL-1β)and aminoguanidine,an inhibitor of nitric oxide synthetase,on insulin release,DNA synthesis and nitric oxide(NO) production of cultured newborn rat islets of Langerhans were studied.The main results were as follows:①IL-1β(10,20,40U/ml)dose-dependently inhibited both insulin release at an acute glucose challenge and 3H-thymidine incorporation,and increased nitrite concentration.The degree of inhibition correlated with the increase of nitrite.②Aminoguanidine(0.1,0.2,0.4mmol/L)dose-dependently inhibited nitrite production,and then alleviated or completely blocked the effects of IL-1βon insulin release and 3H-thymidien incorporation. Our results demonstrated that the cytotoxicity of IL-1βon pancreatic islets was mediated via NO,and that aminoguanidine prevented IL-1β-induced damage to islets of Langerhans by inhibiting NO production.