三氧化二砷对MRL/lpr狼疮鼠IFN-γ、IL-4表达和Th1/Th2平衡的影响  

The Effects of Arsenic Trioxide on Expression of IFN-γ,IL-4 and Th Balance in MRL/lpr Mice

作　　者：王晓冰[1] 陈培荣[1] 张挺[1] 朱小春[1] 周艳[1] 孙莉[1] 陈朝生[1] 

机构地区：[1]温州医学院附属第一医院风湿免疫科,温州325000

出　　处：《细胞生物学杂志》2008年第4期509-514,共6页Chinese Journal of Cell Biology

基　　金：浙江省自然科学基金资助项目(NoM303606)~~

摘　　要：探讨三氧化二砷(ATO)对MRL/lpr狼疮鼠IFN-γ、IL-4表达和Th1/Th2平衡的影响。将发病早期和晚期的MRL/lpr狼疮鼠分别接受ATO、环磷酰胺(CTX)和生理盐水(NS)治疗2个月,然后用ELISA法测血清中IFN-γ、IL-4的浓度和抗ds-DNA抗体水平及四色流式细胞术测脾脏CD3+(T)细胞、CD3+CD4+(Th)细胞、CD3+CD4+IFN-γ+IL-4-(Th1)细胞和CD3+CD4+IL-4+IFN-γ-(Th2)细胞的百分率,从而研究ATO对MRL/lpr狼疮鼠IFN-γ、IL-4表达和Th1/Th2平衡的影响。发现给药后,3、5月龄ATO组MRL/lpr狼疮鼠血清抗ds-DNA抗体水平明显下降(P<0.05),其血清IFN-γ和IL-4浓度、Th1、Th2和CD3+细胞百分率均低于相应月龄的NS组(P<0.05),且NS组中5月龄组Th1/Th2值较3月龄组显著升高(P=0.003),而在ATO组中差异无统计学意义(P=0.187)。因此,研究显示ATO能显著降低发病早期和发病晚期的MRL/lpr狼疮鼠血清抗ds-DNA抗体的水平,可抑制T细胞和Th细胞增生和活化功能,降低IFN-γ和IL-4的血清水平和细胞诱生水平,并在一定程度上逆转发病晚期的MRL/lpr狼疮鼠的Th1偏移。To investigate the effects of arsenic trioxide （ATO） on the expression of IFN-γ, IL-4 and Th balance in MRL/lpr mice in both early and later stage of the disease, young （3-month-old） and old （5-month-old） MRL/lpr mice were chosen for such experiment, each age group was then separated in 3 different sub-groups. The 3 sub-groups of both age groups received arsenic trioxide [ATO, 0.4 mg/（kg·d）], cyclophosphamide [CYC, 50 mg/ （kg·qw）] and sodium chloride （NS, volume weight-determined） abdominal injection respectively for 2 months. Afterwards, serum levels of IFN-γ, and IL-4 were assayed using the mouse cytokines ELISA kit. The rates of the CD3^＋ （T） cells, CD3^＋CD4^＋ （Th） cells and the CD3^＋CD4^＋IFN-γ^＋IL-4^- （Th1） cells CD3^＋CD4^＋IL-4^＋IFN-γ^-（Th2） cells were detected using single-cell measurement of intracellular cytokines by flow cytometry. Results showed that： （1） The production of anti-dsDNA autoantibody was markedly decreased in both of the ATO-treated mice （the young P=0.012, the old P=0.000）, while it was dramatically increased in the NS groups （the young P=0.002, the old P=0.002）. （2） Compared to NS-treated mice, the levels of IFN-γ, IL-4 was dramatically lower in ATO-treated mice （P〈0.05）. （3） The ATO-treated mice had significantly fewer CD3^＋ cells, Th1 and Th2 cells than NS-treated mice （P〈0.05）. ATO-treated young mice had significantly fewer CD3^＋CD4^＋ cells than Ns-treated young mice （P=0.007）. （4） Th1/ Th2 ratio in NS-treated old mice was greater than the young ones （P=0.003）, while there was no significant difference between the two age groups of ATO-treated mice. It was concluded that, ATO can reduce the production of anti-dsDNA autoantibody in both early and later stages of the disease, inhibit the activation and proliferation of both T cells and Th subsets in MRL/lpr mice, decrease the expression of IFN-γ and IL-4, and partly adjust the shifting of 5-month-old MRL/lpr mice to Th1.

关 键 词：三氧化二砷 MRL/lpr狼疮鼠 IFN-γ IL-4 

分 类 号：R593.241[医药卫生—内科学]