17α-己酸羟孕酮对人外周血单个核细胞抵抗地塞米松的逆转作用研究

Reversal effect of 17α-hydroxyprogesterone caproate on dexamethasone resistance in human peripheral blood mononuclear cells

目的探讨17α-己酸羟孕酮对外周血单个核细胞抵抗地塞米松的逆转作用。方法分离健康男性外周血单个核细胞,利用白介素2(IL-2)和IL-4以及植物血凝素刺激外周血单个核细胞,建立地塞米松抵抗的炎症细胞实验模型;单用地塞米松和地塞米松与17α-己酸羟孕酮联合应用于该模型,酶联免疫吸附法检测细胞的IL-2值的改变。结果地塞米松对植物血凝素诱导人外周血产生的IL-2呈现显著的浓度依赖性的抑制作用;用IL-2(13ng·mL-1)和IL-4(6.5ng·mL-1)刺激,再用植物血凝素(15μg·mL-1)刺激外周血单个核细胞可以作为评价地塞米松抵抗的细胞实验模型;在17α-己酸羟孕酮的浓度为10-11,10-10,10-7和10-5 mol·L-1时,可显著提高地塞米松对人外周血产生的IL-2的抑制率,降低地塞米松的IC50(半数抑制浓度)值至少100倍以上。结论 17α-己酸羟孕酮逆转外周血单个核细胞对地塞米松的抵抗,可作为地塞米松等糖皮质激素的增敏剂。

Objective To investigate the reversal effect of 17α-hydroxyprogesterone caproate on dexamethasone resistant in human peripheral blood mononuclear cells .Methods Peripheral blood mononuclear cells （PBMCs） were isolated from healthy volunteers and were stimulated with interleukin-2（IL-2） IL-2 ,IL-4 and phytohemagglutinin to establish a cell study model of dexamethasone （DEX） resistance .By using the model ,PBMCs were stimulated with DEX alone or in combination with 17α-hydroxyprogesterone caproate（17HPC） ,and the IL-2 levels were quantified by enzyme linked immunosorbent assay （ELISA） .Results The production of IL-2 was inhibited by DEX in a significant ,dose-dependent manner .Following the pretreatment with IL-2（13 ng · mL -1 ） and IL-4（6 .5 ng · mL -1 ） ,PBMCs were stimulated with phytohemagglutinin and the experimental model of DEX resistance was estab-lished .The inhibition effects of DEX on the production of IL-2 were enhanced significantly by 17HPC .The IC50 values（50% in-hibitory concentrations） of DEX were decreased at least 100-fold compared to the control （without 17HPC） caused by 10-11 , 10-10 ,10-7 and 10-5 mol · L -1 17HPC .Conclusion 17α-hydroxyprogesterone caproate can reverse dexamethasone resistance in human peripheral blood mononuclear cells and it may be used as a glucocorticoid sensitizer .