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目的研究三氧化二砷(As2O3)对MRL/lpr小鼠免疫功能和肾脏组织病理变化的影响。方法45只MRL/lpr狼疮小鼠ip给予环磷酰胺50 mg·kg-1(每周1次)和As2O30.8 mg·kg-1,每天1次,共2个月。用ELISA法检测血清抗双链DNA(dsDNA)抗体、干扰素γ(IFN-γ)和白细胞介素12(IL-12)浓度;用流式细胞术测定脾CD3+,CD19+,CD3+CD4+和CD3+CD8+细胞亚群的百分比;用PAS染色法观察肾组织病理变化;用免疫荧光方法检测肾组织IgG和补体C3的表达。结果与给药前比较,给药2个月后,正常对照组血清抗dsDNA抗体水平升高,由给药前1.18±0.26升高至1.80±0.26(P<0.01),As2O3和环磷酰胺组该抗体水平明显降低,分别由给药前1.14±0.58和1.09±0.22降低至0.92±0.06和0.67±0.14(P<0.05,P<0.01)。与正常对照组比较:①As2O3和环磷酰胺组血清抗ds-DNA抗体、IFN-γ和IL-12浓度明显降低(P<0.05),环磷酰胺组抗ds-DNA抗体比As2O3组显著降低(P<0.01);②As2O3组CD3+,CD3+CD4+和CD19+细胞百分率明显降低(P<0.01),环磷酰胺组CD3+,CD3+CD8+和CD19+细胞百分率明显降低(P<0.01);As2O3组CD3+CD4+细胞百分率明显降低(P<0.01);③As2O3和环磷酰胺组小鼠肾小球细胞计数和活动度积分明显降低(P<0.05,P<0.01),As2O3和环磷酰胺组无显著差异;④As2O3和环磷酰胺组肾IgG表达明显降低(P<0.05),补体C3表达无明显差异,As2O3和环磷酰胺组之间无显著性差异。结论As2O3能降低MRL/lpr狼疮小鼠血清抗ds-DNA抗体水平,抑制T,B和Th细胞活化和增殖,降低血清IFN-γ和IL-12水平,从而缓解狼疮肾炎的病理变化。
Objective To study the effect of arsenic trioxide (As2O3) on immune function and pathological changes of kidney in MRL / lpr mice. Methods Forty five MRL / lpr lupus mice were given cyclophosphamide 50 mg · kg-1 (once a week) and As2O30.8 mg · kg-1 once a day for 2 months. Serum anti-dsDNA antibody, interferon γ (IFN-γ) and interleukin-12 (IL-12) were detected by ELISA. The levels of CD3 +, CD19 +, CD3 + + CD8 + cell subsets; PAS staining was used to observe the pathological changes of renal tissue; Immunofluorescence was used to detect the expression of IgG and complement C3 in renal tissue. Results Compared with those before administration, the levels of serum anti-dsDNA antibody in the normal control group increased from 1.18 ± 0.26 to 1.80 ± 0.26 (P <0.01) before administration, and the levels of As2O3 and cyclophosphamide The level of antibody was significantly decreased from 1.14 ± 0.58 and 1.09 ± 0.22 before administration to 0.92 ± 0.06 and 0.67 ± 0.14, respectively (P <0.05, P <0.01). Compared with the normal control group, the serum anti-dsDNA antibodies, IFN-γ and IL-12 concentrations in As2O3 and cyclophosphamide groups were significantly decreased (P <0.05), and the anti-dsDNA antibodies in cyclophosphamide group were significantly lower than those in As2O3 group (P <0.01). The percentage of CD3 +, CD3 +, CD4 + and CD19 + cells in As2O3 group was significantly decreased (P <0.01), the percentage of CD3 +, CD3 + CD8 + and CD19 + cells in cyclophosphamide group was significantly decreased (P <0.01). ③Compared with As2O3 and cyclophosphamide groups, glomerular cell counts and activity scores decreased obviously (P <0.05, P <0.01), while there was no significant difference between As2O3 and cyclophosphamide groups And cyclophosphamide (P <0.05). There was no significant difference in complement C3 expression between the two groups. There was no significant difference between As2O3 and cyclophosphamide groups. Conclusion As2O3 can reduce the level of serum anti-dsDNA antibody in MRL / lpr lupus mice, inhibit the activation and proliferation of T, B and Th cells and decrease the serum levels of IFN-γ and IL-12, thereby alleviating the pathological changes of lupus nephritis.