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作 者:史伟 史敦绘 王丽霞[2] 娄方明 锁星星 陆萍[2] 李晶[1] 汤郁[1] Shi Wei;Shi Dunhui;Wang Lixia;Lou Fangming;Suo Xingxing;Lu Ping;Li Jing;Tang Yu(Department of Rheumatology,the Affiliated Hospital of Jiangsu University,Zhenjiang 212001.China;Department of Hematology,the Affiliated Hospital of Jiangsu University,Zhenjiang 212001.China)
机构地区:[1]江苏大学附属医院风湿免疫科,江苏镇江212001 [2]江苏大学附属医院血液科,江苏镇江212001
出 处:《南京医科大学学报(自然科学版)》2019年第4期485-490,512,共7页Journal of Nanjing Medical University(Natural Sciences)
基 金:国家自然科学基金(81571582);江苏省高层次卫生人才"六个一工程"拔尖人才项目(LGY2017101)
摘 要:目的:研究同种异体骨髓间充质干细胞(bone marrow mesenchymal stem cell,BMMSCs)输注对MRL/lpr狼疮鼠造血的影响,为BMMSCs输注治疗系统性红斑狼疮(systemic lupus erythematosus,SLE)的血液系统损伤提供依据。方法:分离培养C57BL/6小鼠的BMMSCs并对MRL/lpr狼疮鼠进行静脉输注,同时以PBS为对照。分为对照(C57BL/6)组、狼疮鼠(MRL/lpr)组、BMMSCs输注组1(MRL/lpr鼠12周注射BMMSCs)、PBS对照组1(MRL/lpr鼠12周注射PBS)、BMMSCs输注组2(MRL/lpr鼠12、16周两次注射BMMSCs)、PBS对照组2(MRL/lpr鼠12、16周两次注射PBS)。在20周末取小鼠的外周血进行血细胞计数,后4组取骨髓及脾脏进行流式细胞术和甲基纤维素半固体集落形成试验(CFU)检测分析输注组和对照组骨髓及脾脏各系细胞比例。结果:与C57BL/6小鼠相比,狼疮鼠外周血红细胞计数[(9.3±0.8)×1012个/L vs.(10.5±0.8)×1012个/L,n=5,P <0.001]、血红蛋白[(138.1±11.6)g/L vs.(156.4±11.0)g/L,n=5,P <0.001]和血小板计数[(695.3±136.2)×109个/L vs.(844.1±180.8)×109个/L,n=5,P<0.05]降低,与PBS对照组相比,BMMSCs输注组MRL/lpr狼疮鼠血小板数量改善[(795.0±75.7)×109个/L vs.(593.4±123.4)×109个/L,n=5,P <0.05],骨髓中干细胞(n=5,P <0.001)和成熟T细胞比例减少(n=5,P <0.05),髓系比例增加(n=5,P <0.01),pre-B数量有所改善(n=5,P <0.05),脾脏内干细胞比例上升(n=5,P <0.05),成熟T细胞比例下降(n=5,P <0.05)。结论:BMMSCs输注对狼疮鼠外周血、骨髓及脾脏不同系造血细胞有影响,其对狼疮鼠的血液系统损伤有治疗意义。Objective:To investigate the effect of bone marrow mesenchymal stem cells(BMMSCs)infusion on hematopoiesis in MRL/lpr mice,and provide a basis for the infusion of BMMSCs to treat systemic lupus erythematosus(SLE)blood system damage.Methods:BMMSCs of C57 BL/6 mice were isolated and cultured for intravenous infusion of MRL/lpr mice. The experimental group was divided into:①C57 BL/6 mice group;②MRL/lpr mice group;③once PBS control group:12 weeks injection of PBS lupus mice group;④once BMMSCs infusion group:12 weeks injection of BMMSCs lupus mice group;⑤twice PBS control group:12 and 16 weeks were injected with PBS lupus mice group;⑥twice BMMSCs infusion group:12 and 16 weeks were injected BMMSCs lupus mice group.Blood cells were counted in peripheral blood of lupus mice at 20 weeks. Bone marrow and spleen were taken for flow cytometry and methylcellulose semi-solid colony formation assay(CFU). Results:Compared with C57 BL/6 mice,the peripheral blood erythrocyte count,hemoglobin and platelet count of lupus mice were decreased. Compared with the PBS control group,the number of platelets in the BMMSCs infusion group was improved,the proportion of stem cells and mature T cells in the bone marrow was decreased,the proportion of myeloid cells was increased,the number of pre-B was improved. The proportion of stem cells in the spleen was increased,the proportion of T cells decreased. Conclusion:BMMSCs infusion has effects on peripheral blood,bone marrow and spleen hematopoietic cells of MRL/lpr mice. It has therapeutic effect on the blood system injury of lupus mice.
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