同种异体骨髓间充质干细胞输注对MRL/lpr狼疮鼠肾脏CXCL12/CXCR4表达的影响  

Effects of allogeneic bone marrow mesenchymal stem cells infusion on the expression of CXCL12/CXCR4 in the kidney of MRL/lpr lupus mice

作　　者：程孟微 汤郁[1] 马翠 史伟 郑文娟 裘影影[1] 芮金兵[1] 王燕茹[1] Cheng Mengwei;Tang Yu;Ma Cui;Shi Wei;Zheng Wenjuan;Qiu Yingying;Rui Jinbing;Wang Yanru(Department of Rheumatology and Immunology,Affiliated Hospital of Jiangsu University,Zhenjiang 212000,Jiangsu Province,China)

机构地区：[1]江苏大学附属医院风湿免疫科,江苏省镇江市212000

出　　处：《中国组织工程研究》2022年第19期3018-3023,共6页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金(81571582),项目负责人:汤郁;江苏省高层次卫生人才“六个一工程”拔尖人才(LGY2017101),项目负责人:汤郁。

摘　　要：背景:趋化因子CXCL12及其受体CXCR4在狼疮肾炎的发病中起到一定作用,探究骨髓间充质干细胞对狼疮小鼠肾脏CXCL12/CXCR4表达的影响对于进一步研究狼疮肾炎的发病机制以及骨髓间充质干细胞对狼疮肾炎的治疗机制有一定意义。目的:探讨同种异体骨髓间充质干细胞输注对MRL/lpr狼疮鼠外周血和肾脏CXCL12/CXCR4表达的影响。方法:分离培养C57BL/6小鼠骨髓间充质干细胞,扩增至第3代,细胞浓度为1×10^(9) L^(-1)。选取四五周龄雌性MRL/lpr小鼠15只,分为MRL/lpr组(未进行尾静脉输注)、PBS组(12周龄末注射PBS)、骨髓间充质干细胞组(12周龄末注射骨髓间充质干细胞),每组5只,另选取5只C57BL/6小鼠为正常对照。各组小鼠在20周龄末处死,采用ELISA法检测各组小鼠外周血血浆中CXCL12的表达;流式细胞分析外周血、肾脏中B淋巴细胞表面CXCR4的表达;免疫组化染色观察肾脏中CXCL12的表达;苏木精-伊红染色观察肾脏病理变化。结果与结论:(1)与C57BL/6组相比,MRL/lpr组狼疮鼠外周血血浆和肾脏中CXCL12表达增高,且外周血以及肾脏B淋巴细胞表面CXCR4的表达均增高;(2)与PBS组相比,骨髓间充质干细胞组狼疮鼠外周血血浆和肾脏中CXCL12表达降低,且外周血以及肾脏B淋巴细胞表面CXCR4的表达均降低;(3)苏木精-伊红染色观察输注骨髓间充质干细胞后狼疮鼠肾脏炎症改善;(4)结果表明,MRL/lpr狼疮鼠肾脏中存在CXCL12/CXCR4表达异常,骨髓间充质干细胞输注可能通过影响CXCL12/CXCR4的表达从而起治疗作用。BACKGROUND:Chemokine CXCL12 and its receptor CXCR4 play a certain role in the pathogenesis of lupus nephritis,and it is of significance to explore the effect of bone marrow mesenchymal stem cells infusion on the expression of CXCL12/CXCR4 in lupus kidney for further study of the pathogenesis of lupus nephritis and the mechanism of bone marrow mesenchymal stem cells in the treatment of lupus nephritis.OBJECTIVE:To investigate the effect of allogeneic bone marrow mesenchymal stem cell infusion on the expression of CXCL12/CXCR4 in the kidney of MRL/lpr lupus mice.METHODS:Bone marrow mesenchymal stem cells of C57 BL/6 mice were isolated and cultured,expanded to the third passage,and the cell concentration was 1×10^(9)L^(-1).Totally 15 female MRL/lpr mice aged four to five weeks were selected and divided into MRL/lpr group(no tail vein infusion),PBS group(PBS injection at the end of 12 weeks),and bone marrow mesenchymal stem cell group(injection of bone marrow mesenchymal stem cells at the end of 12 weeks)(n=5 per group).An additional five C57 BL/6 mice were selected as normal controls.Mice in each group were sacrificed at the end of 20 weeks of age.The expression of CXCL12 in peripheral blood plasma was detected by ELISA.The expression of CXCR4 on B lymphocyte surface in peripheral blood and kidney was analyzed by flow cytometry.The expression of CXCL12 in the kidney was demonstrated by immunohistochemistry.The pathological changes of the kidney tissue were observed by hematoxylin-eosin staining.RESULTS AND CONCLUSION:(1)Compared with the C57 BL/6 group,the expression of CXCL12 in peripheral blood plasma and kidney was increased,and the expression of CXCR4 on B lymphocyte surface in peripheral blood and kidney was also increased in the MRL/lpr group.(2)Compared with PBS group,the expression levels of CXCL12 in peripheral blood plasma and kidney of lupus mice were decreased,and CXCR4 expression levels on the surface of B lymphocytes in peripheral blood and kidney of lupus mice were similarly decreased in the bone mar

关 键 词：干细胞 骨髓间充质干细胞 狼疮肾炎 系统性红斑狼疮 趋化因子 CXCL12 CXCR4 

分 类 号：R459.9[医药卫生—治疗学] R392.4[医药卫生—临床医学]