【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。更多还原

【Abstract】 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.更多还原