胰岛素对人巨噬细胞肿瘤坏死因子-α蛋白表达分泌的影响

目的　探讨胰岛素对人巨噬细胞肿瘤坏死因子 α(TNF α)蛋白表达分泌的影响以及普伐他汀对其的作用。方法　将佛波酯加入人单核细胞白血病细胞株THP 1细胞培养液中诱导其形成巨噬细胞后 ,加入不同浓度的胰岛素、普伐他汀及甲羟戊酸继续培养 4 8h ,观察人巨噬细胞中TNF α蛋白表达水平及细胞培养上清液中TNF α蛋白水平。结果　胰岛素可诱导人巨噬细胞及其培养上清液中TNF α蛋白水平显著升高 ,且呈剂量依赖性 ,加入普伐他汀后可使胰岛素刺激的人巨噬细胞中及其培养上清液中TNF α蛋白水平显著下降 ,普伐他汀的这种作用可被甲羟戊酸所抑制。结论　普伐他汀对糖尿病患者心血管系统的保护作用可能部分与其抑制胰岛素介导的炎症反应有关。

The effects of insulin on expression and secretion of TNF-α protein by human macrophages and the effects of pravastatin

Objective To investigate the effects of insulin on expression and secretion of TNF α protein by human macrophages and the effects of pravastatin.Methods The human monocytic leukemia cell line THP 1 cells were cultured and then phorbol 12 myristate 13 acetate was added to induce differentiation of the THP 1 cells into macrophages.The resulting cells were cultured in RPMI 1640 medium.Human insulin,pravasatatin and mevalonate were added and the cells were cultured further for 48 h.The levels of TNF α protein in cells and in supernatant were tested by Western blot and ELISA assay.Results Insulin stimulation resulted in significantly elevated levels of TNF α protein in macrophages and the supernatant of cell culture in dose dependent manner,however,after incubation with insulin plus pravastatin,the levels of TNF α protein in cells and the supernatant decreased and this effect of pravastatin could be diminished by added mevalonate.Conclusion Insulin can increase the expression and secretion of TNF α protein by human macrophages and the effects can be inhibited by pravastatin,indicating that the cardio protective effects of pravastatin on diabetic patients might be partially associated with inhibiting inflammation mediated by insulin.