胰岛素对VEC增殖过程中FKBP12基因表达的影响

Effects of different concentrations of insulin on the expression of insulin receptor and its mRNA levels in vascular endothelial cell proliferation

目的 通过不同浓度胰岛素对血管内皮细胞 (vascularendothelialcell ,VEC)增殖过程中胰岛素受体 (insulinre ceptor ,InsR)和FK5 0 6结合蛋白 12 (FK5 0 6bindingprotein 12 ,FKBP12 )及其基因表达等的影响 ,初步探讨VEC的胰岛素抵抗。方法 在内皮细胞生长因子 (endothelialcellgrowthfactor ,ECGF)作用下 ,培养大鼠VEC并传代。检测VEC在增殖过程中不同浓度胰岛素对VEC的InsR和FKBP12及其基因表达、生长曲线和细胞上清液一氧化氮 (nitrogenmonoxide ,NO)含量等的影响。结果 与对照组相比 ,1U/ml胰岛素组VEC的InsR和FKBP12mRNA表达降低 ;生长曲线向右下偏移且对数生长期延迟 ;细胞上清液NO含量下降。结论 VEC是胰岛素敏感细胞 ;当培养液中胰岛素浓度为 1U/ml时 ,经 16h的培养后 ,可使VEC对生理浓度胰岛素的反应性降低 ,该胰岛素抵抗状态至少维持 2 4h。FKBP12可能是与VEC胰岛素抵抗相关的重要信息分子。

Objective To study the insulin resistance in vascular endothelial cells (VECs) by observing the effects of different concentrations of insulin on the expression of insulin receptor (InsR) and FK506 binding protein 12 (FKBP12) and their mRNA expression in VEC proliferation. Methods Rat VECs were cultured with enzyme digestion method and were identified by using immuocytochemical methods with factor Ⅷ antibody. The expressions of InsR mRNA and FKBP12 mRNA were detected by semi quantitative RT PCR. The effects of different concentrations of insulin on the expression of InsR, the growth rate of VEC, and the content of nitrogen monoxide (NO) in culture medium were also detected. Results Compared with those in the control group, the expressions of InsRmRNA and FKBP12 mRNA decreased and VEC proliferation and NO production in culture medium were inhibited in 1 U/ml insulin group. Conclusion VECs exposed to 1 U/ml insulin for 16 h may be able to induce a state of insulin resistance which could be maintained for at least 24 h. FKBP12 may play a critical role in insulin resistance of VECs.