摘要
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 investigate the effect of arsenic trioxide （As2 03 ） on immune function and renal pathology in MRL/lpr mice. METHODS Forty-five MRL/lpr mice were divided into control, As203 0.8 mg.kg-1 （ip, once a day） and cyclophosphamide 50 mg＇kg-1 （ip, once a week） groups. After continuously administration for 2 months, the serum level of anti-double stranded-DNA （dsDNA） autoantibody, interferon-y （IFN-r） and interleukin-12（IL-12） of mice was measured with ELISA. The subsets of the spleen lymphocytes were detected with flow cytometry. The kidney was removed for periodic acid Schiff dyeing. The expression of IgG and complement C3 in the nephridial tissue was observed by immunofluorescence assay. RESULTS Two months after therapy, compared with that of before treatment, the anti-dsDNA antibody level in normal control group increased from 1.18±0.26 to 1.80 ± 0.26 （ P 〈 0.01 ）, while it significantly decreased from 1.14 ± 0.58 to 0.92 ± 0.06 in As203 grouP and from 1.09± 0.22 to 0.67±0. 14 in cyclophosphamide group, respectively （ P 〈 0.05, P 〈 0.01 ）. Compared with normal control group ： ① the serum levels of the anti-dsDNA antibody, IFN-y and IL-12 in As203 and cyclophosphamide groups were lower than those of normal control group （P 〈0. 05 ,P 〈0.01 ） , and the anti-dsDNA antibody level was much lower in cyclophosphamide group than As203 group （P 〈 0.01 ） ; ② percent- age of CD3 ＋ , CD19 ＋ and CD3 ＋CD4＋cells in As203 group was lower than normal control group （P 〈0.01 ）, the percentage of CD3 ＋ , CD3 ＋CD8 ＋ and CD19 ＋ cells in cyclophosphamide group was much lower than normal control group （P 〈 0.01 ）, CD3 ＋CD4 ＋ cells in As203 group were fewer than cyclophosphamide group （ P 〈 0.01 ） ; ③ the glomerulus cell count per glomerular cross-sections and the integral of activity in As203 and cyclophosphamide groups were less than normal control group （ P 〈 0. 05, P 〈 0.01 ） , while there was no significant differ
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2012年第6期794-800,共7页
Chinese Journal of Pharmacology and Toxicology
基金
The project supported by National Natural Science Foundation of China(31100576)
Key Scientific and Technological Project of Wenzhou City(Y20090240)
Scientific and Technological Project of Wenzhou City(Y20100287)~~
