骨髓间充质干细胞对肾病综合征大鼠CD4^+CD25^+调节性T细胞的影响

Effects of bone marrow mesenchymal stem cell transplantation on CD4^+CD25^+ regulatory T cells in rats with primary nephrotic syndrome

背景:CD4+CD25+调节性T细胞功能降低、数量下降已被公认为是肾病综合征患儿免疫失调的重要表现。骨髓间充质干细胞具有免疫调节功能,可上调CD4+CD25+调节性T细胞,抑制淋巴细胞增殖,并已在许多免疫性疾病方面成功应用。目的:观察骨髓间充质干细胞移植对原发性肾病综合征大鼠外周血CD4+CD25+调节性T细胞的影响。方法:自SD大鼠分离骨髓间充质干细胞,经体外传代培养及鉴定后制备细胞悬液。30只SD大鼠随机均分为3组,生理盐水组和干细胞移植组尾静脉注射阿霉素建立阿霉素肾病大鼠模型,干细胞移植组注射阿霉素当日尾静脉射干细胞1×107;正常组不做处理。结果与结论:①与正常组比较,生理盐水组大鼠均出现肾病综合征表现,以腹水、大量蛋白尿、低蛋白血症、高胆固醇血症为特征;干细胞移植组较生理盐水移植组则有明显改善(P<0.05)。②造模第28天,干细胞移植组和生理盐水组大鼠造模后外周血CD4+CD25+Treg/CD4+Treg均明显高于正常组(P<0.05);干细胞移植组与生理盐水组比较差异无显著性意义(P>0.05)。③造模第28天,干细胞移植组大鼠外周血单个核细胞FoxP3mRNA的表达显著高于生理盐水组和正常组(P<0.05)。提示骨髓间充质干细胞移植对阿霉素肾病综合征模型有一定的治疗作用,其机制可能与上调FoxP3在组织局部的表达而诱导CD4+CD25+Treg产生有关。

BACKGROUND：Decreased function and reduced number of CD4＋CD25＋regulatory T cells have been considered the major manifestation of immunity dysfunction in children with primary nephrotic syndrome. Bone marrow mesenchymal stem cells have immunoregulation effects, which up-regulate CD4＋CD25＋regulatory T cells, inhibit proliferation of lymphocytes, and have been widely used in many immune diseases. OBJECTIVE：To investigate the effects of bone marrow mesenchymal stem celltransplantation on the CD4＋CD25＋regulatory T cells of peripheral blood in rats with primary nephrotic syndrome. METHODS：Bone marrow mesenchymal stem cells from six Sprague-Dawley rats were isolated, passaged and utilized for cellsuspension preparation. At the third passage, bone marrow mesenchymal stem cells were used for transplantation. The remaining 30 rats were randomly and equal y divided into three groups：normal group, normal saline infusion group, and bone marrow mesenchymal stem cells group. The rat models of primary nephrotic syndrome were established by single injection of adriamycin intravenously through tail vein in the latter two groups. Rats were then treated with bone marrow mesenchymal stem cells （1＆#215;10 7 ） （bone marrow mesenchymal stem cells group） or normal saline （normal saline infusion group） through tail vein at the same time after adriamycin administration. The normal group received no treatment. RESULTS AND CONCLUSION：Compared with the normal group, rats in the normal saline infusion group developed nephropathy characterized by ascites, proteinuria, hypoalbuminemia, hypercholastero-lnemia, and progressive renal injury. However, the proteinurine and clinical severity in bone marrow mesenchymal stem cells group were significantly ameliorated after treatment with bone marrow mesenchymal stem cells.＆amp;nbsp;CD4＋CD25＋Treg/CD4＋Treg in the peripheral blood in the bone marrow mesenchymal stem cells group and normal saline infusion group were significantly higher than that in the normal group at 28 days after model establishment （P＆lt;0.05）, while there was no significant difference between bone marrow mesenchymal stem cells group and normal saline infusion group （P＆gt;0.05）. The expression of FoxP3 mRNA in the peripheral blood mononuclear cells of the bone marrow mesenchymal stem cells group was significantly higher than that in the normal saline infusion group and normal group （P＆lt;0.05）. The bone marrow mesenchymal stem cells play a protective effect in rats with primary nephrotic syndrome, which may be related to the increase of local expression of FoxP3 and generation of CD4＋CD25＋Treg.