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目的探讨三氧化二砷(arsenic trioxide,ATO)对MRL/lpr狼疮鼠淋巴细胞亚群和细胞因子表达的影响。方法MRL/lpr狼疮鼠随机分为ATO组(0.4mg·kg-1·d-1,ip)、环磷酰胺(CTX)组(50mg·kg-1每周1次,ip)和生理盐水(NS)组(按体重取量,ip),给药2个月。取脾脏制成脾细胞悬液,加入佛波醇酯(PMA)和ionomycin活化,同时加monensin抑制蛋白转运,于37℃,5%CO2培养4h后,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)细胞内细胞因子IFN-γ、IL-4、IL-10和IL-12的水平;分离血清,用ELISA法测血清中抗ds-DNA抗体、IFN-γ、IL-4、IL-10和IL-12的浓度。结果①给药后,ATO组小鼠血清的抗ds-DNA抗体水平较给药前明显下降(P<0.01),而NS对照组则明显升高(P<0.05)。②ATO组CD3+细胞和CD3+CD4+百分率均显著低于NS组(P<0.01);③ATO组的血清IFN-γ和IL-12浓度均低于NS组(前者P<0.01,后者P=0.018);④ATO组Th细胞内IFN-γ、IL-4、IL-10和IL-12表达均显著低于NS组(P<0.01)。结论三氧化二砷能显著降低MRL/lpr狼疮鼠血清抗ds-DNA抗体的水平,抑制T细胞和Th细胞增生和活化功能,降低IFN-γ和IL-12的血清水平和Th细胞内IFN-γ、IL-4、IL-10和IL-12的水平。
Objective To investigate the effect of arsenic trioxide (ATO) on the lymphocyte subsets and cytokine expression in MRL/lpr lupus mice. Methods MRL/lpr lupus mice were randomly divided into ATO group (0.4 mg·kg-1·d-1, ip), cyclophosphamide (CTX) group (50 mg·kg-1 weekly, ip) and saline ( NS) group (by weight, ip), administered for 2 months. The spleen cells were made from the spleen and added with phorbol ester (PMA) and ionomycin. At the same time, monensin was added to inhibit protein transport. After cultured at 37° C. and 5% CO2 for 4 h, splenic CD3+ was measured by four-color flow cytometry. Percentage of T) cells and CD3+CD4+ (Th) cells and levels of cytokines IFN-γ, IL-4, IL-10 and IL-12 in CD3+CD4+ (Th) cells; serum was isolated and serum was measured by ELISA The concentration of anti-ds-DNA antibodies, IFN-γ, IL-4, IL-10, and IL-12. Results 1 After administration, the anti-ds-DNA antibody level in the serum of ATO group was significantly lower than that before administration (P<0.01), while it was significantly higher in the NS control group (P<0.05). 2 The percentage of CD3+ cells and CD3+CD4+ in ATO group were significantly lower than those in NS group (P<0.01); the concentrations of serum IFN-γ and IL-12 in ATO group were lower than those in NS group (P<0.01 for the former and P=0.018 for the latter) The expression of IFN-γ, IL-4, IL-10 and IL-12 in Th cells of 4ATO group was significantly lower than that of NS group (P<0.01). Conclusion Arsenic trioxide can significantly reduce the level of anti-ds-DNA antibodies in serum of MRL/lpr lupus mice, inhibit the proliferation and activation of T cells and Th cells, and reduce the serum levels of IFN-γ and IL-12 and IFN-γ and IL in Th cells. -4, IL-10 and IL-12 levels.