三氧化二砷对炎症细胞的影响及其分子机制

目的观察三氧化二砷(As2O3)对人T淋巴细胞和人树突状细胞(DCs)凋亡以及对树突状细胞表型、细胞因子分泌的影响,探索As2O3洗脱支架局部抗炎作用的有关机制。方法分离培养人T淋巴细胞,用rhGM-CSF和rhIL-4诱导单个核细胞分化为树突状细胞,流式细胞仪检测As2O3对T淋巴细胞和树突状细胞凋亡的影响;用LPS诱导树突状细胞分化成熟,流式细胞仪检测As2O3干预对树突状细胞成熟表型的影响,ELISA检测As2O3对树突状细胞分泌细胞因子的影响。结果 As2O3在1umol/L浓度时即可明显诱导人T淋巴细胞凋亡,在5umol/L浓度时可诱导树突状细胞凋亡,且均呈剂量依赖性;As2O3在低于凋亡诱导剂量时即可抑制LPS诱导的树突状细胞成熟,下调树突状细胞表面分子CD83和CD86的表达率,并减少树突状细胞IL-10、IL-12和IFN-γ等细胞因子的释放。结论 As2O3具有诱导T淋巴细胞、树突状细胞凋亡以及抑制树突状细胞的免疫成熟的作用,As2O3洗脱支架的局部抗炎作用和As2O3的上述作用有关。

Effect and Molecular Mechanism of Arsenic Trioxide on Inflammatory Cells

Objective Arsenic trioxide（As2O3） eluting stent has the effect to inhibit inflammatory reaction in the section of stented coronary arteries in porcine coronary artery injury model.The aim of this study is to observe the effect of As2O3 on apoptosis of T lymphocyte cells and on apoptosis,phenotype and cytokine production of dendritic cells（DCs）.Method Human monocytes were purified with Anti-CD14 microbeads and cultured in DMEM containing GM-CSF and IL-4 for 5 days to generate immature DCs.Cells were stimulated by As2O3 for 48 hours,the apoptotic T lymphocyte cells and DCs,phenotypic change of DCs were analyzed by flow cytometry,and the cytokine production of DCs was determined by ELISA.Results As2O3 dose-dependently induced the apoptosis of human T lymphocyte and DCs and inhibited the maturation of DCs below apoptosisinduced dose（3umol/L） by reducing expression of CD83,CD86 and cytokine production of IL10,IL12,IFN-γ.Conclusion The role of As2O3 in T lymphocyte and DCs is associated to the effect of As2O3 eluting stent on inhibition of inflammatory reaction in the section of stented porcine coronary arteries.