三氧化二砷对rIL-13诱导肺成纤维细胞增殖和炎性介质表达的影响

摘要

目的 探讨三氧化二砷(As2O3)的抗肺纤维化机制.方法 将体外培养的肺成纤维NIH3T3细胞株随机分为对照组及观察组,对照组仅予DMEM培养基,观察组予80 ng/ml重组白细胞介素(rIL)-13及不同浓度As2O3处理24、48 h.MTT法检测细胞增殖;原位杂交方法检测巨噬细胞炎症蛋白(MCP)-1α mRNA表达;放射免疫法检测细胞培养上清液IL-6、IL-8水平.结果 As2O3处理后细胞增殖明显受抑,且呈时间和剂量依赖性(P＜0.01);rIL-13处理后细胞MCP-1α mRNA和IL-6、IL-8表达增强,联用As2O3后此作用明显受抑(P＜0.01).结论 As2O3可能通过抑制rIL-13诱导的肺成纤维细胞增殖及炎性介质表达而发挥抗肺纤维化作用.%Objective To explore the mechanism of anti-pulmonary fibrosis by arsenic trioxide( As2O3 ). Methods NIH3T3 fibroblasts line cultured in vitro were divided into observed group 1, observed group 2, observed group 3 and control group, then the observed groups were treated with recombinant interleukin (rlL) -13 of 80 ng/ml and As2O3 of 2, 4 μmol/L, the control group were treated with DMEM oaly. MTI assay was used to study cell proliferation; the levels of MIP-1 α mRNA in NIH3T3 fibroblasts were detected by in situ hybridization; the concentrations of IL-6, IL-8 were deter mined by radioimmunoassay. Results As2O3 treatment significantly inhibited fibroblast proliferation in a time-and dosedependent manner (P ＜ 0.01 ). Compared with the control group, rlL-13 enhanced the expression of IL-6, IL-8 and MIP1α mRNA of fibroblasts, and As2O3 inhibited the above roles of rlL-13 (P ＜ 0.01 ). Conclusions As2O3 may play important roles in delaying the development of pulmonary fibrosis by inhibiting fibroblasts proliferation and expression of inflammatory mediators induced by IL-13.