亚砷酸对狼疮鼠自身抗体和白细胞介素-1012表达的影响

The effects of arsenic trioxide on the expression of autoantibody and interleukin-10, interleukin-12 in MRL/lpr mice

目的探讨亚砷酸（ATO）对狼疮鼠自身抗体和白细胞介素（IL）-10、IL-12表达的影响。方法MRL／lpr狼疮鼠随机分为ATO组、环磷酰胺（CTX）组和生理盐水（NS）组，给药2个月。用四色流式细胞术测脾脏CD3＋（T）细胞和CD3＋CD4＋（Th）细胞的百分率以及CD3＋CD4＋（Th）细胞内IL-10和IL-12的水平；用酶联免疫吸附试验（ELISA）法测血清中抗双链DNA（dsDNA）抗体、IL-10和IL-12的浓度。分别采用单因素方差分析、LSD检验，配对t检验进行统计学处理。结果①给药后ATO组小鼠血清的抗dsDNA抗体水平吸光度值（A）0．92±0．06，较给药前1．14±0．58明显下降（P〈0．01）；②ATO组CD3＋细胞和CD3＋CD4＋百分率[分别为（44±4）％和（20±4）％]均显著均低于Ns组水平[分别为（59v5）％和（30±3）％]（P〈0．01）；③ATO组的血清IL-12浓度（84±12）pg／ml较NS组水平（103±13）pg／ml显著降低（P=0．018）；④ATO组Th细胞内IL-10和IL-12的表达水平（1．5±0．4）％和（2．43±0．42）％显著低于Ns组（2．5±0．5）％和（3．24±0．40）％（P〈0．01）。结论亚砷酸能显著降低MRL／lpr狼疮鼠血清抗dsDNA抗体的水平，抑制T细胞和Th细胞增生和活化功能，降低IL—12的血清水平和Th细胞的诱生水平，及能降低IL-10的Th细胞的诱生水平。

Objective To investigate the effects of arsenic trioxide （ATO） on the expression of autoan-tibody and interleukin （IL）-10 IL-12 in MRL/lpr mice, Methods MRL/lpr mice wereseparated into 3 different groups. The 3 groups received arsenic trioxide （ATO, 0.4 mg/kg l.d i）, eyelophosphamide （CTX, 50 mg/kg） and sodium chloride （NS, volume welght-determined） abdominal injection respec-tively. The treatment stopped 2 months later. Afterwards, the rates of CD3＋（T） cells, CD3＋CD4＋（Th） ceils and the CD3＋ CD4＋cells which produced IL-10 and IL-12 were detected using single-cell measurement of intr-aeellular cytokines by flow eytometry after polyelonal stimulation with PMA and ionomyein for 4 hours in 5% CO2. Serum levels of IL-10 and IL-12 were assessed using the Mouse eytokines ELISA Kit. One-way ANOVA LSD test and paires t test were used for statistical analysis. Results （1） The level of anti-dsDNA antibody after treatment was 0.92±0.06, while it was 1.14±0.58 before treatment. So the ds-DNA antibody level was significantly decreased in ATO group （P〈0.01）, while it was dramatically increased in the NS groups （P〈0.05） after the treatment; （2） ATO group had significantly less CD3＋ cells and CD3＋CD4＋ cells [ （44±4）% and （20±4）%]compared with NS group [（59±5）% and （30±3）%] （P〈0.01）. （3） The serum level of IL-12 in the ATO group was （84±12） pg/ml, while it was （103±13） pg/ml in the NS group （P=0.018）. ＋ The intraeellular levels of IL-10 and IL-12 produced by CD3＋CD4＋ （Th） cells in the ATO group were （1.5±0.4）% and （2.43± 0.42）%, which was significantly lower than those in the NS group respectively （2.5±0.5）% and （3.24±0.40）% （P〈0.01）. Conclusion Arsenic trioxide can reduce the production of anti-dsDNA antibody,inhibit the activation and proliferation of both T cells and Th subsets in the MRL/Ipr mice, and hence decrease the serum levels of IL-12 and the levels of IL-10, IL-12 produced by Th cells.