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MRL/lpr狼疮鼠骨髓间充质干细胞表面粘附分子N-钙粘附蛋白表达增高并伴有骨髓中B淋巴细胞生成障碍

Increment of N-cadherin Expression in Bone Marrow Mesenchymal Stem Cells Accompanies by Imparment of Bone Marrow B Lymphocyte Production in MRL/lpr Lupus Mice

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【作者】 王丽霞陆化费小明汤郁史伟陆萍朱彦

【Author】 WANG Li-Xia;LU Hua;FEI Xiao-Ming;TANG Yu;SHI Wei;LU Ping;ZHU Yan;Department of Hematology, The First Affiliated Hospital of Nanjing Medical University;Department of Hematology, Affiliated Hospital of Jiangsu University;Department of Reumatology, Affiliated Hospital of Jiangsu University;

【通讯作者】 陆化;

【机构】 南京医科大学第一附属医院血液科江苏大学附属医院血液科江苏大学附属医院风湿科

【摘要】 目的:观察MRL/lpr狼疮鼠骨髓的血液生成情况及骨髓微环境中骨髓间充质干细胞(bone marrow masenchymal stem cell,BMMSC)表面的粘附分子N-钙粘附蛋白(N-cadherin)的表达水平。方法:采集MRL/lpr狼疮鼠外周血进行血细胞计数;流式细胞术检测和分析狼疮鼠骨髓各系血细胞的比例;甲基纤维素半固体集落形成试验(CFU)检测狼疮鼠骨髓中CFU-pre-B、BFU-E、CFU-GM数目。分离培养狼疮鼠的BMMSC,Western blot检测其N-cadherin的表达。最后,分别用BMP/Smad通路的激动剂BMP-2和抑制剂Noggin处理BMMSC,尔后观察狼疮鼠BMMSC的N-cadherin的表达变化。结果:与C57BL/6小鼠比较,狼疮鼠的血红蛋白、红细胞计数和血细胞比容显著降低(P<0.01;n=7);狼疮鼠骨髓中B220+细胞比例和CFU-pre-B数目均明显下降(P<0.05;n=5)。狼疮鼠BMMSC的粘附分子N-cadherin的表达水平明显高于对照组(P<0.05;n=3)。BMP-2处理狼疮鼠BMMSC后N-cadherin的水平下降,而在Noggin处理后N-cadherin表达则上调(P<0.05;n=3)。结论:MRL/lpr狼疮小鼠骨髓中B淋巴细胞生成障碍。此外,小鼠骨髓微环境中BMMSC表面的粘附分子N-cadherin水平升高,其可能参与了MRL/lpr狼疮小鼠的骨髓血液生成异常。

【Abstract】 Objective: To investigate the hematological changes in MRL/lpr lupus mice and detect N-cadherin expression in their bone marrow mesenchymal stem cell(BMMSC). Methods: Peripheral blood cell count was analyzed.The ratio of each lineage in bone marrow was analyzed by flow cytometry. Bone marrow CFU-pre-B, BFU-E and CFUGM were detected by colony formation assay. Expression of N-cadherin in BMMSC was analyzed by Western blot before and after treatment with the BMP/Smad pathway aganist BMP-2 and inhibitor Noggin. Results: Hemoglobin, red blood cell count and hematocrit decreased in lupus mice, compared with C57 BL/6 mice. The ratio of B220+ lymphocyte and the number of CFU-pre-B in bone marrow of lupus mice decreased. Expression of N-cadherin in BMMSC of lupus mice was higher than that in the control group. Expression of N-cadherin decreased in BMP-2-treated BMMSC and increased after Noggin treatment. Conclusion: Hematological changes in lupus mice include anemia and impairment of bone marrow B cell production. The expression of N-cadherin in BMMSC of lupus mice increases which maybe involved in abnormal hemogenesis in MRI/Ipr lupus mice.

【基金】 国家自然科学基金(81571582);镇江市重点研发计划(社会发展)项目(SH2018067)
  • 【文献出处】 中国实验血液学杂志 ,Journal of Experimental Hematology , 编辑部邮箱 ,2019年03期
  • 【分类号】R593.241
  • 【被引频次】4
  • 【下载频次】108
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