B7-1人-鼠嵌合抗体对小鼠狼疮样肾炎模型的免疫干预效应  

Immune intervention effect of human-mouse chimeric antibody B7-1 against murine lupus nephritis model

作　　者：沈辉[1] 朱玉强[1] 孔永[1] 王婧[1] 朱华亭[1] 於葛华[1] 蔡磊[1] 朱莹[1] 王志瑶[1] 邱玉华[1] 

机构地区：[1]苏州大学医学部免疫学系,苏州215123

出　　处：《中国免疫学杂志》2015年第9期1200-1205,共6页Chinese Journal of Immunology

基　　金：国家自然科学基金项目(81373236)资助

摘　　要：目的:在运用化学法建立小鼠狼疮样肾炎模型并对其进行生物学鉴定的基础上,探讨B7-1人-鼠嵌合抗体阻断B7/D28信号通路对小鼠狼疮样肾炎模型病理损伤的逆转效应。方法:取6周龄雌性C57BL/6J小鼠,予一次性腹腔注射Pristane 0.5ml/只,每月定期检测小鼠的尿蛋白、ANA及肾脏病理学改变。取尿蛋白含量达到++,ANA荧光强度达到++的小鼠随机分为3组,每组5只。抗体干预组用B7-1人-鼠嵌合抗体经眼眶静脉序贯给药,阳性对照组注射免疫抑制剂CTX,阴性对照组注射人同型Ig G。每月定期检测尿蛋白及ANA,干预至3个月时,处死小鼠,取肾脏进行H&E染色分析,免疫复合物(IC)检测及透射电镜观察。结果:Pristane诱导至4个月时,80%的小鼠尿蛋白含量达到+^+++,血清ANA荧光强度为++^+++,出现尿蛋白及ANA的小鼠,其肾小球炎性细胞侵润,肾小管上皮样细胞可见水肿样变性、血管充血明显,纤维组织增生。抗体干预后,尿蛋白逐渐由++^+++降为±^++,ANA由++^+++降为+^++。与阴性对照组比较具有统计学差异(P<0.01)。肾脏HE染色分析的结果显示,抗体干预组肾小球炎性细胞侵润及肾小管充血等表现均得到明显改善。免疫荧光染色可见抗体干预组抗原抗体复合物(IC)的荧光强度明显减弱。经透射电镜观察,抗体干预组与阴性对照组相比,肾小球的电子致密物沉积减少,基底膜厚度趋于均匀。结论:B7-1抗体通过抑制B7-1/CD28信号通路下调机体的免疫应答,减少自身抗体的产生,对自身免疫造成的病理损伤具有逆转作用。Objective：On the basis of the use of chemical methods to establish mouse model of lupus nephritis and its biological identification , we investigate the reverse effect of pathological lesions of B 7-1 human-mouse chimeric antibody blockade against B7/D28 signaling pathway in mice with lupus nephritis model.Methods：Pristane was injected intraperitoneally to 6-week-old female C57BL/6J mice at dose of 0.5 ml per mouse in one go,and urine protein,ANA and renal pathological changes were detected on a monthly basis.Mice whose urine protein content reached ＋＋and ANA fluorescence intensity reached ＋＋were randomly devided into three groups ,five each.Antibody intervention group was sequentially injected with B 7-1-mouse chimeric antibody by orbital venous , positive control group was injected with immunosuppressant CTX , negative control group was injected with isotype control IgG.Urine protein and ANA were also detected on a monthly basis.Mice were sacrificed three months after intervention was executed.Kidney was used for H＆E dying , IC detection and electric microscope observation.Results： After four-month Pristane induction , urine protein content of 80%mice reached ＋-＋＋＋,meanwhile,serum ANA fluorescence intensity reached ＋＋-＋＋＋.Glomerulonephritis infiltrating cells were observed Mice with urine protein and ANA , glomerular inflammatory cell infiltration , tubular epithelial cell degeneration visible edema ,vascular congestion significantly ,fibrosis.After antibody intervention ,urine protein content in antibody intervention group gradually reduced from ＋＋-＋＋＋to ±-＋＋＋,ANA ＋＋-＋＋＋to ＋-＋＋,and were significantly different from that in the negative control group （ P〈0.01 ）.Analysis of kidney H＆E dying showed that antibody glomerular infiltration of inflammatory cells in the intervention group and tubular congestion and other symptoms were improved significantly.Immunofluorescence staining indicated that fluorescence intensity of IC was significantly

关 键 词：B7-1 人-鼠嵌合抗体 降植烷 狼疮样肾炎 尿蛋白 抗核抗体 

分 类 号：R392.1[医药卫生—免疫学]