西洛酰胺对IL-1β诱导损伤的离体胰岛细胞的防护作用及其机制

Protective effect of phosphodiesterase inhibitor on interleukin-1β induced destruction of isolated rat pancreatic islet cells and its mechanism

目的探讨磷酸二酯酶(phosphodiesterase,PDE)抑制剂对白细胞介素-1β(IL-1β)诱导损伤的离体雄性Wistar大鼠胰岛细胞的防护作用及其机制。方法采用离体培养的雄性Wistar大鼠胰岛细胞,分别检测IL-1β(30u/mL)及IL-1β与特异性Ⅲ型PDE抑制剂西洛酰胺(cilostamide,CIL)对胰岛细胞亚硝酸盐合成、胰岛素(Ins)分泌、环磷酸腺苷(cAMP)水平及细胞活性(MTT)的影响。结果以IL-1β诱导,离体雄性Wistar大鼠胰岛细胞亚硝酸盐合成显著增加,cAMP水平、Ins分泌及MTT值显著降低(P<0.001),而CIL能阻断这些作用(P<0.01),且具有显著剂量依赖性(r2=0.44,P<0.01)。结论CIL能够保护IL-1β诱导的离体鼠胰岛细胞损伤。

[Objective] To observe the protective effect of phosphodiesterase (PDE) inhibitor on interlenkin-1β(IL-1β) induced destruction of isolated rat pancreatic islet cells and its mechanism. [Methods] Isolated pancreatic islet cells from Wistar rats were cultured in vitro. Nitrite production, cAMP levels, insulin secreation and cell activity (MTT assay) in rat pancreatic islet cells incubated with IL-1β (30 U/mL), the specific PDE Ⅲ inhibitor cilostamide( CIL) singly and in combination, were measured. [Results] IL-1βinduced significant increase in nitrite production, decreased cAMP levels, insulin secreation and MTT assay (P <0.001), which were blocked by CIL (P <0.01), and the inhibition of NO production gradually enhanced by the increase of the concentration of CIL. Linear regression and t-test indicate CIL suppresses NO production in a dose-dependent manner (r2=0.44, P <0.01). [Conclusion] The results suggest that CIL can protect IL-1β-induced damage to islets .