慢性移植物抗宿主病狼疮样肾炎小鼠模型的研制
作者：阳晓 叶任高 陈伟英 魏毅 许韩师 李幼姬
单位：阳晓 叶任高 陈伟英 许韩师 李幼姬(510080 广州，中山医科大学第一附属医院肾内科卫生部肾脏病临床研究重点实验室)；魏毅(第一军医大学中医系)
关键词：移植物抗宿主病(GVHD)；狼疮肾炎；疾病模型，动物
中华肾脏病杂志000501摘 要：目的研制可诱导的、耗时较短的慢性移植物抗宿主病(GVHD)狼疮样肾炎小鼠模型。方法无菌分离母体DBA/2小鼠淋巴细胞，注入雌性(C57BL/10R×DBA/2)F1杂交鼠。观察16周。结果注射后8周模型小鼠以肾小球细胞增生为主要特征，未见蛋白尿及间质损害；注射后12周以大量蛋白尿、低蛋白血症、水肿及高脂血症为其主要症状，病理以肾小球系膜增宽、基底膜节段性增厚、肾间质细胞浸润为特点；至注射后16周则以肾功能损害为主要改变，病理以肾小球基质大量增生，肾间质纤维化为主要特征。血清学示抗dsDNA抗体阳性，免疫荧光示免疫球蛋白及补体沿系膜(IgM)和毛细血管(IgG、C3)沉积及电镜可见上皮下电子致密物沉积提示本模型符合LN的特点。结论慢性GVHD狼疮样小鼠模型病理改变类似人类狼疮肾炎(LN)，且省时、变异小，病变呈明显的阶段性。该模型为研究LN的发病机制、预防和治疗提供了良好的工具。
, 百拇医药
Chronic graft-versus-host disease induces murine lupus nephritis model
YANG Xiao ,YE Rengao ,CHEN Weiying,et al.
(Department of Nephrology,Key Clinical Kidney Research Institute of Ministry of Health,First Affiliated Hospital,Sun Yat-sen University of Medical Sciences,Guangzhou 510080,China)
Abstract：Objective To establish chronic graft-versus-host disease (GVHD) inducing murine lupus nephritis(LN) model.Methods (C57BL/10×DBA/2) F1 hybrids were used as recipients of DBA/2 donor lymphoeytes.Single cell suspensions were injected intravenously 4 times at 3～4 days intervals. Results Eight weeks after injection of lymphocytes,the glomerular cells increased significantly,and no cast and protein appeared in urine.At twelfth week,glomerular mesangial segmental proliferation,extracellular matrix expansion and interstitial damage exhibited.Albuminuria aggravated markedly in affected animals,causing hypoalbuminemia,hyperlipidemia and edema.At sixteenth week,global glomerular sclerosis appeared and uremia developed.Deposits of immunoglobulins were observed along the glomerular capillary wall and in the mesangium.Electron microscopy revealed the presence of subepithelial electron-dense deposits.Anti-dsDNA autoantibody titers increased significantly during 8 to 16 weeks after GVHD induction.Conclusion The murine model is comparable to the lesions characterizing human LN and offers an excellent model for studies on the pathogenesis,prevention and treatment of LN.
, 百拇医药
Keywords：Graft-versus-host disease (GVHD);Lupus nephritis;Disease model,animal 基金项目：国家自然科学基金资助项目 (39970933和39870721)；中山医科大学211重点科研基金资助项目(98150)；广东省自然科学基金资助项目(990073)
参考文献：
[1]Bruijn JA,Van Elevn EH,Hogendoorn PCW,et al.Murine chronic graft-versus-host disease as a model for lupus nephritis.Am J Path,1988,130:639-640.
[2]Sutmuller M,Baelde HJ,Tysma OMH,et al.Experimental glomernlonephritis is attenuated by CD8+ T cell chimerism and prevented by mis-1-incompatible thymocytes.Clin Immunol Immunopathol,1998,88:114-122.
, 百拇医药
[3]Floege J,Aalpers CE,Burns MW,el al.Glomerular cells,extracellular matrix accumulation,and the development of glomerulosclerosis in the remnant kidney model,Lab Invest,1992,66:485-497.
[4]Austin H,Muenz L,Joyce KM,et al.Diffuse proliferative lupus nephritis:identification of specific pathologic features affecting renal outcome. Kidney Ink 1984, 25:689-695.
[5]Via CS,Sharrow SO,Shearer GM.Role of cytotoxic T lymphocytes in the prevention of lupus-like disease occuring in a murine rondel of graft-versus-host disease.J Immunol,1987,139:1840-1849.
, 百拇医药
[6]Via CS,Shearer GM.T-cell interactions in autoimmunity:insights from a murine model of graft-versus-host disease.Immunol Today,1988,9:207-213.
[7]Bruijn JA,Hogendoorn PCW,Corver WE,et al.P.0athogenesis of experimental lupus nephritis:a role for anti-basement membrane and anti-tubular brush border antibodies in murine chronic graft-versus-host disease.Clin Exp Immunol,1990.79:115-123.
[8]Bruijn JA,Vanleer EHG,Heer DE,et al.Charaeterization and in vivo transfer of nephritogenic autobodies directod against dipeptidyl peptidase Ⅳ and laminin in experimental lupus nephritis.Lab Invest,1990,63:350-359.
[9]Bruijn JA,Bergijk EC,Heer DE,et al.Induction and progression of experimental lupus nephritis:exploration of pathogenetic pathway.Kidney Int,1992,41:5-13.
收稿日期：2000-01-09, http://www.100md.com
单位：阳晓 叶任高 陈伟英 许韩师 李幼姬(510080 广州，中山医科大学第一附属医院肾内科卫生部肾脏病临床研究重点实验室)；魏毅(第一军医大学中医系)
关键词：移植物抗宿主病(GVHD)；狼疮肾炎；疾病模型，动物
中华肾脏病杂志000501摘 要：目的研制可诱导的、耗时较短的慢性移植物抗宿主病(GVHD)狼疮样肾炎小鼠模型。方法无菌分离母体DBA/2小鼠淋巴细胞，注入雌性(C57BL/10R×DBA/2)F1杂交鼠。观察16周。结果注射后8周模型小鼠以肾小球细胞增生为主要特征，未见蛋白尿及间质损害；注射后12周以大量蛋白尿、低蛋白血症、水肿及高脂血症为其主要症状，病理以肾小球系膜增宽、基底膜节段性增厚、肾间质细胞浸润为特点；至注射后16周则以肾功能损害为主要改变，病理以肾小球基质大量增生，肾间质纤维化为主要特征。血清学示抗dsDNA抗体阳性，免疫荧光示免疫球蛋白及补体沿系膜(IgM)和毛细血管(IgG、C3)沉积及电镜可见上皮下电子致密物沉积提示本模型符合LN的特点。结论慢性GVHD狼疮样小鼠模型病理改变类似人类狼疮肾炎(LN)，且省时、变异小，病变呈明显的阶段性。该模型为研究LN的发病机制、预防和治疗提供了良好的工具。
, 百拇医药
Chronic graft-versus-host disease induces murine lupus nephritis model
YANG Xiao ,YE Rengao ,CHEN Weiying,et al.
(Department of Nephrology,Key Clinical Kidney Research Institute of Ministry of Health,First Affiliated Hospital,Sun Yat-sen University of Medical Sciences,Guangzhou 510080,China)
Abstract：Objective To establish chronic graft-versus-host disease (GVHD) inducing murine lupus nephritis(LN) model.Methods (C57BL/10×DBA/2) F1 hybrids were used as recipients of DBA/2 donor lymphoeytes.Single cell suspensions were injected intravenously 4 times at 3～4 days intervals. Results Eight weeks after injection of lymphocytes,the glomerular cells increased significantly,and no cast and protein appeared in urine.At twelfth week,glomerular mesangial segmental proliferation,extracellular matrix expansion and interstitial damage exhibited.Albuminuria aggravated markedly in affected animals,causing hypoalbuminemia,hyperlipidemia and edema.At sixteenth week,global glomerular sclerosis appeared and uremia developed.Deposits of immunoglobulins were observed along the glomerular capillary wall and in the mesangium.Electron microscopy revealed the presence of subepithelial electron-dense deposits.Anti-dsDNA autoantibody titers increased significantly during 8 to 16 weeks after GVHD induction.Conclusion The murine model is comparable to the lesions characterizing human LN and offers an excellent model for studies on the pathogenesis,prevention and treatment of LN.
, 百拇医药
Keywords：Graft-versus-host disease (GVHD);Lupus nephritis;Disease model,animal 基金项目：国家自然科学基金资助项目 (39970933和39870721)；中山医科大学211重点科研基金资助项目(98150)；广东省自然科学基金资助项目(990073)
参考文献：
[1]Bruijn JA,Van Elevn EH,Hogendoorn PCW,et al.Murine chronic graft-versus-host disease as a model for lupus nephritis.Am J Path,1988,130:639-640.
[2]Sutmuller M,Baelde HJ,Tysma OMH,et al.Experimental glomernlonephritis is attenuated by CD8+ T cell chimerism and prevented by mis-1-incompatible thymocytes.Clin Immunol Immunopathol,1998,88:114-122.
, 百拇医药
[3]Floege J,Aalpers CE,Burns MW,el al.Glomerular cells,extracellular matrix accumulation,and the development of glomerulosclerosis in the remnant kidney model,Lab Invest,1992,66:485-497.
[4]Austin H,Muenz L,Joyce KM,et al.Diffuse proliferative lupus nephritis:identification of specific pathologic features affecting renal outcome. Kidney Ink 1984, 25:689-695.
[5]Via CS,Sharrow SO,Shearer GM.Role of cytotoxic T lymphocytes in the prevention of lupus-like disease occuring in a murine rondel of graft-versus-host disease.J Immunol,1987,139:1840-1849.
, 百拇医药
[6]Via CS,Shearer GM.T-cell interactions in autoimmunity:insights from a murine model of graft-versus-host disease.Immunol Today,1988,9:207-213.
[7]Bruijn JA,Hogendoorn PCW,Corver WE,et al.P.0athogenesis of experimental lupus nephritis:a role for anti-basement membrane and anti-tubular brush border antibodies in murine chronic graft-versus-host disease.Clin Exp Immunol,1990.79:115-123.
[8]Bruijn JA,Vanleer EHG,Heer DE,et al.Charaeterization and in vivo transfer of nephritogenic autobodies directod against dipeptidyl peptidase Ⅳ and laminin in experimental lupus nephritis.Lab Invest,1990,63:350-359.
[9]Bruijn JA,Bergijk EC,Heer DE,et al.Induction and progression of experimental lupus nephritis:exploration of pathogenetic pathway.Kidney Int,1992,41:5-13.
收稿日期：2000-01-09, http://www.100md.com