骨髓间充质干细胞移植治疗系统性红斑狼疮  

Bone marrow mesenchymal stem cell transplantation for the treatment of systemic lupus erythematosus

作　　者：王治国[1] 刘学明[2] 佟胜全[1] 石哲群[1] 饶莉[1] 

机构地区：[1]河北医科大学附属唐山工人医院风湿免疫科,河北省唐山市063000 [2]河北医科大学附属唐山工人医院神经内科,河北省唐山市063000

出　　处：《中国组织工程研究》2016年第10期1461-1467,共7页Chinese Journal of Tissue Engineering Research

基　　金：河北省医学科学研究重点课题计划(20150948)~~

摘　　要：背景:目前对系统性红斑狼疮患者治疗一般采用非特异性免疫抑制方法,但是预后存在易感染、复发率高等问题。目的:评价骨髓间充质干细胞对系统性红斑狼疮小鼠的治疗作用。方法:16只系统性红斑狼疮小鼠随机平均分为对照组与实验组,实验组小鼠经尾静脉注射移植第3代骨髓间充质干细胞,对照组注射等量的生理盐水。收集小鼠尿液采用Bradford法检测尿蛋白水平,采集两组小鼠尾尖血液,利用放射免疫方法测定血清抗ds-DNA抗体浓度;组织学切片进行苏木精-伊红染色及免疫组化学染色,显微镜下观察小鼠肾脏病理学改变,采用流式细胞仪检测眼内眦血液、新鲜脾脏与胸腺中CD4^+CD25^+T细胞水平。结果与结论:(1)骨髓间充质干细胞移植后10周内,两组MRL/LPR小鼠尿液中尿蛋白均逐渐升高,对照组尿蛋白升高速率明显高于实验组,从第4周至第10周,实验组小鼠尿蛋白水平明显低于对照组(P<0.05)。(2)对照组小鼠肾脏组织被淋巴细胞浸润,出现少量的浆细胞,表现出间质性肾炎病理,实验组小鼠无肾脏病理改变。(3)对照组与实验组小鼠的肾小球系膜区域均呈现出免疫复合物,对照组呈片状分布,实验组呈点状分布,相对所占面积比例明显低于对照组。(4)实验组小鼠血液和胸腺内CD4^+CD25^+T细胞水平明显高于对照组(P<0.05);实验组小鼠脾脏CD4^+CD25^+T细胞水平略高于对照组小鼠,但差异无显著性意义(P>0.05)。(5)实验组小鼠血清抗ds-DNA抗体浓度明显低于对照组(P<0.05)。(6)结果提示骨髓间充质干细胞移植可改善系统性红斑狼疮小鼠的病理损伤,对系统性红斑狼疮疾病具有一定的治疗效果。BACKGROUND： The non-specific immune suppression method is generally used for treatment of systemic lupus erythematosus, but poor prognosis, such as infection and high recurrence rate, exists. OBJECTIVE： To evaluate the therapeutic effect of bone marrow mesenchymal stem cell transplantation on systemic lupus erythematosus in mice. METHODS： Sixteen mice with systemic lupus erythematosus were equivalently randomized into control and experimental groups, or then subjected to passage 3 bone marrow mesenchymal stem cell transplantation or the equal volume of normal saline via the tail vein, respectively. Mouse urine samples were collected to detect urine protein levels by Bradford method. Blood samples from the tip of the mouse tail were extracted to detect serum anti-ds-DNS antibody concentration by radioimmunoassay. Mouse kidney tissues were taken and observed pathohistologically through hematoxylin-eosin staining and immunohistochemistry staining under microscope. Flow cytometry was used to detect the expression of CD4^＋CD25^＋T cells in the inner canthus blood, fresh spleen and thymus. RESULTS AND CONCLUSION： Within 10 weeks after cell transplantation, the urine protein levels in the two groups were gradually increased, and the rising velocity was higher in the control group than in the experimental group. From the 4th to 10 th week, the urine protein levels in the experimental group were significantly lower than those in the control group（P〈0.05）. In the control group, lymphocyte infiltration was visible in the kidney tissues with a few of plasmocytes, and pathological findings showed the mice presented with interstitial nephritis; in the experimental group, the mice had no pathological changes in the kidney. In the two groups, immune complexes were found in the mesangial area, which showed a patch-like distribution in the control group and a punctate distribution in the experimental group; the relative proportion of the occupied area in the experimental group was significantly lower than that in

关 键 词：干细胞 移植 系统性红斑狼疮 MRL/LPR小鼠 骨髓间充质干细胞 干细胞移植 CD4^+CD25^+T细胞水平 血清ds-DNA抗体 

分 类 号：R394.2[医药卫生—医学遗传学]