三氧化二砷对系统性红斑狼疮患者外周血淋巴细胞凋亡和IL-10分泌的影响

Effects of arsenic trioxide on apoptosis and interleukin-10 release of Peripheral blood lymphocyte in systemic lupus erythematosus

目的观察不同浓度三氧化二砷(As2O3)对活动期系统性红斑狼疮(SLE)患者外周血淋巴细胞凋亡及白介素10(IL-10)分泌的影响。方法收集15例未曾用过激素及免疫抑制剂治疗并排除其它类型的自身免疫性疾病及感染性疾病的初诊SLE患者和同期15例健康体检者(健康对照组)的外周血,分别于不同浓度As2O3干预培养后12 h和24 h采用Vnnexin V\PI染色定量分析外周血淋巴细胞凋亡率,采用酶联免疫吸附法(ELISA)检测培养上清液中IL-10的含量。结果 SLE组患者和健康对照组在不同As2O3浓度下12 h和24h的凋亡率均增加(P<0.05);不同浓度As2O3诱导SLE患者在12 h和24 h淋巴细胞凋亡率明显高于健康对照组(P<0.05);且随As2O3干预浓度的增加,两组外周血淋巴细胞凋亡率均增加(P<0.05)。SLE组患者外周血淋巴细胞在体外培养后分泌IL-10水平明显高于健康对照组(P<0.05),且As2O3能显著抑制其分泌,As2O3对健康对照组无影响(P>0.05)。结论 As2O3能诱导外周血淋巴细胞凋亡,并且具有时间和浓度依赖性,提示As2O3通过引起淋巴细胞凋亡发挥治疗作用;As2O3抑制SLE患者外周血淋巴细胞分泌IL-10可能是其发挥治疗作用的重要机制之一。

Objective To investigate the effects of different concentration of the apoptosis induced effect and secretary function of As2O3 on peripheral blood lymphocyte in systemic lupus erythematosus （SLE） patients. Methods Collecting 15 cases never used hormone treatment and immunosuppressive agents,and exclusion of other types of autoimmune diseases and infectious disease in newly diagnosed SLE patients and 15 cases of healthy subjects （healthy controls） in peripheral blood; and the two groups were treated with different concentration of As2O3 ,the apoptosis rate was calculated and analysized after 12 and 24 hours by flow cytometry （FCM） of vnnexin V／PI. Interleukin-10（IL-10） in supernatant liquid were measured with ELISA. Results As2Oa can induce apoptosis of peripheral blood lymphocyte of SLE patients and healthy subjects. The effect is gradually increasing along with the increasing of concentrations of AszO3 and treated time. The apoptosis rate of both the SLE group and the control group increased accordingly. The apoptosis rate of the two groups with different concentration of As2O3 were different. In both group, As2O3 can evoke significant increase of apoptosis rate （P〈0.05）. Compared with control group, secretion of IL-10 by peripheral blood lymphocyte of SLE group were higher in vitro, which can be suppressed by As2O3, and was not observed in control group （P〉0. 05）. Conclusion As2O3 can induce apoptosis in peripheral blood lymphocytes,and has a time and concentration dependent, suggesting that As2O3 induced by lymphocyte apoptosis play a therapeutic role; As2O3 suppressor SLE lymphocytes in peripheral blood of patients with secretory IL-10 may play its therapeutic effect is one of the important mechanisms.