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

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）-1αmRNA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-1αmRNA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。

Effects of arsenic trioxide on NIH3T3 fibroblasts proliferation and expression of inflammatory mediators induced by interleukin-13

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（rIL）-13 of 80 ng/ml and As2O3 of 2,4 μmol/L,the control group were treated with DMEM only.MTT assay was used to study cell proliferation;the levels of MIP-1α mRNA in NIH3T3 fibroblasts were detected by in situ hybridization;the concentrations of IL-6,IL-8 were determined by radioimmunoassay.Results As2O3 treatment significantly inhibited fibroblast proliferation in a time-and dose-dependent manner（P〈0.01）.Compared with the control group,rIL-13 enhanced the expression of IL-6,IL-8 and MIP-1α mRNA of fibroblasts,and As2O3 inhibited the above roles of rIL-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.