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慢性移植物抗宿主病狼疮样肾炎小鼠模型的研制

Chronic graft-versus-host disease induces murine lupus nephritis model

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【作者】 阳晓叶任高陈伟英魏毅许韩师李幼姬关伟民余学清

【Author】 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)

【机构】 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!广州510080第一军医大学中医系中山医科大学第

【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/10 × 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。

【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 lymphocytes. 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 of offers an excellent model for studies on the pathogenesis, prevention and treatment of LN.

【基金】 国家自然科学基金!(39970933和39870721);中山医科大学211重点科研基金!(98150);广东省自然科学基金
  • 【文献出处】 中华肾脏病杂志 ,Chinese Journal of Nephrology , 编辑部邮箱 ,2000年05期
  • 【分类号】R-332
  • 【被引频次】55
  • 【下载频次】285
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