【摘要】 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。更多还原

【Abstract】 OBJECTIVE To investigate the effects of arsenic trioxide(ATO) on expression of cytokines and lymphocyte subsets proliferation in splenic cells of MRL/lpr mice.METHODS MRL/lpr mice were divided into 3 different groups.The 3 groups received arsenic trioxide(ATO,0.4 mg·kg-1·d-1),cyclophosphamide(CTX,50 mg·kg-1·qw-1) and sodium chloride respectively.The treatment was lasted for 2 months.The contents of the CD3+(T)cells,CD3+CD4+(Th)cells and the IL-4,IL-10 and IL-12 were detected using single-cell measurement of intracellular cytokines by flow cytometry after polyclonal stimulation with PMA and ionomycin for 4 h in 5% CO2.Serum levels of IFN-γ,and IL-4 were assayed using the Mouse cytokines ELISA Kit.RESULTS ① The production of ds-DNA antibody was significantly decreased in ATO group(P<0.01),while it was dramatically increased in the NS groups(P<0.05) after the treatment.②Compared with NS group,CD3+cells and CD3+CD4+cells in ATO group were decreased significantly(P<0.01).③The serum levels of IFN-γ and IL-12 were significantly reduced in ATO group(P<0.01 and P=0.018).④T he intracellular levels of IFN-γ,IL-4,L-10 and IL-12 produced by CD3+CD4+(Th)cells in ATO group were significantly lower than those in NS group(P<0.01).CONCLUSION Arsenic trioxide can reduce the production of ds-DNA antibody,inhibit the activation and proliferation of both T cells and Th subsets in MRL/lpr mice,and hence decrease the serum levels of IFN-γ,IL-12 and the levels of IFN-γ,IL-4,IL-10 and IL-12 yielded by Th cells.更多还原