褪黑素抑制白介素-1β诱导的人脐静脉内皮细胞通透性

摘要

Objective To determine the effect of melatonin (MLT) on interleukin-1β ( IL-1β )-induced vascular permeability.Methods Human umbilical vein endothelial cells (HUVECs) were exposed to IL-1β with or without MLT and endothelial cell permeability was assessed by measuring the flux of FITC-dextran across the HUVEC monolayer.Results IL-1β increased the relative permeability of HUVECs from 1.5 ± 0.1 to 4.8 ± 0.3, 5.2 ± 0.4 and 9.8 ±0.8 (P ＜0.01 ); MLT ( 10 and 100 μmol/L) attenuated IL-1β ( 10 ng/mL) induced permeability from 5.2 ±0.4 to 2.8 ±0.3 and 2.7 ±0.3 (P ＜0.Ol ).Melatonin improved IL-1β-induced disruption of VE-cadherin adherens junctions.The relative expression of VE-cadherin decreased from 0.91 ± 0.04 in control group to O.42 ±0.05 in IL-1β group (P ＜0.01) and increased to 0.69 ±0.04 in MLT group (P ＜0.01 compared with IL-1β group), though still lower than control (P ＜ 0.05 ).Conclusion Our data indicate that MLT may strengthen the barrier integrity of HUVECs through attenuating the change of VE-cadherin.%目的 观察褪黑素(MLT)对自介素-1B(IL-1β)诱导的内皮通透性改变的影响.方法 用不同浓度的IL-1β和MLT干预人脐静脉内皮细胞(HUVECs).用Transwell系统检测透过单层HUVECs的荧光标记的葡聚糖.用免疫荧光和Western blot检测HUVECs钙黏素(VE-cadhefin)的表达.结果 与对照组相比,5、10和20ng/mL的IL-1β分别使HUVECs通透性由1.5±0.1升高为4.8±0.3、5.2±0.4和9.8±0.8(P＜0.01);10和100 μmol/L的MLT分别使10 ng/mL的IL-1β诱导的通透性从5.2±0.4降至2.8±0.3和2.7±0.3(P＜0.01).IL-1β破坏VE-cadherin在细胞膜上表达的连续性,MLT抑制IL-1β的这种作用.与对照组相比,IL-1β使HUVECs的VE-cadherin表达量由0.91±0.04降至0.42±0.05(P＜0.01).MLT可使其表达量上调至0.69±0.04,显著高于IL-1β组(P＜0.01),但仍低于对照组(P＜0.01).结论 MLT能够通过抑制IL-1β诱导的VE-cadherin表达的降低来保护人脐静脉内皮细胞屏障的完整性.