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三氧化二砷对MRL/Ipr小鼠免疫功能和肾组织病理变化的影响
  • ISSN号:1000-3002
  • 期刊名称:《中国药理学与毒理学杂志》
  • 时间:0
  • 分类:R994.6[医药卫生—毒理学;医药卫生—药学] R967[医药卫生—药理学;医药卫生—药学]
  • 作者机构:[1]附属第一医院风湿免疫科、温州医学院, [2]分子医学实验室, [3]附属第一医院呼吸科,浙江温州325035
  • 相关基金:国家自然科学基金(31100576);温州市科技计划重点项目(Y20090240);温州市科技计划(Y20100287)
中文摘要:

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50mg·kg-1(每周1次)和As2030.8mg·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1(IFN-1)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-r和IL-12浓度明显降低(P〈0.05),环磷酰胺组抗ds-DNA抗体比As203组显著降低(P〈0.01);②As203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;④As:O,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-y和IL-12水平,从而缓解狼疮肾炎的病理变化。

英文摘要:

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

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期刊信息
  • 《中国药理学与毒理学杂志》
  • 北大核心期刊(2011版)
  • 主管单位:军事医学科学院
  • 主办单位:军事医学科学院毒物药物研究所 中国药理学会 中国毒理学会
  • 主编:张永祥
  • 地址:北京市海淀区太平路27号
  • 邮编:100850
  • 邮箱:cjpt518@163.com
  • 电话:010-68276743
  • 国际标准刊号:ISSN:1000-3002
  • 国内统一刊号:ISSN:11-1155/R
  • 邮发代号:82-140
  • 获奖情况:
  • 国内外数据库收录:
  • 美国化学文摘(网络版),英国农业与生物科学研究中心文摘,波兰哥白尼索引,荷兰文摘与引文数据库,荷兰医学文摘,美国剑桥科学文摘,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),中国北大核心期刊(2000版)
  • 被引量:9749