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骨髓源间充质干细胞注射疗法对肝硬化大鼠模型免疫系统的调节作用及其相关机制研究
Effects of bone marrow mesenchymal stem cells therapy on immunological function in liver cirrhosis rats
【摘要】 目的探讨骨髓间充质干细胞移植治疗对肝硬化大鼠自身免疫功能的影响,为临床治疗方法提供理论依据。方法选取150只健康雄性Wistar大鼠,随机分为3组,即对照组(不采取任何干预措施)、肝硬化组(行大鼠肝硬化模型制备)、治疗组(行大鼠肝硬化模型制备后给予骨髓间充质干细胞移植治疗)。检测各组大鼠脾脏T、B淋巴细胞增殖情况,CD4~+CD25~+Foxp3~+调节性T细胞的水平,Foxp3 mRNA表达水平。结果对照组大鼠肝细胞结构完整,没有纤维增生及假小叶存在;肝硬化组大鼠肝小叶结构破坏,假小叶出现,肝细胞水肿变性坏死,可见炎性细胞浸润;实验组大鼠肝细胞水肿变性坏死程度较肝硬化组显著降低,但仍可见增生的纤维组织。肝硬化组大鼠脾脏T、B淋巴细胞体外增殖情况明显高于对照组(P<0.05),经BMSCs治疗后,治疗组大鼠脾脏T、B淋巴细胞体外增殖情况显著低于肝硬化组(P<0.05);肝硬化组大鼠脾脏Foxp3 mRNA的表达水平明显低于对照组(P<0.05),经BMSCs治疗后,治疗组脾脏Foxp3 mRNA的表达水平高于肝硬化组(P<0.05);肝硬化组大鼠脾脏CD4~+CD25~+Foxp3~+调节性T细胞百分比明显低于正常组(P<0.05),经BMSCs治疗后,治疗组脾脏CD4~+CD25~+调节性T细胞百分比高于肝硬化组(P<0.05)。结论骨髓间充质干细胞移植治疗可通过抑制脾脏T、B淋巴细胞增殖,升高CD4~+CD25~+Foxp3~+调节性T细胞及Foxp3 mRNA表达水平,影响自身免疫功能,从而影响疾病的转归。
【Abstract】 This study performed to investigate the effect of bone marrow mesenchymal stem cells onimmunocyte in immune organ of liver cirrhosis rat, by detecting the proliferation of lymphocyte, expression of Foxp3 mRNA and the level of CD4~+CD25~+Foxp3~+T cell, thereby explaining the mechanism of immunoloregulation of bonemarrow mesenchymal stem cells in vivo. Total of 150 male Wistar rats were randomly divided into 3 groups: thecontrol group, the liver cirrhosis group, and the treatment group. And then the proliferation of lymphocyte, theexpression of Foxp3 mRNA and the level of CD4~+CD25~+Foxp3~+T cell were detect in all groups. Microscopy showedthat the liver cells were arranging tidy, and there were no fiber hyperplasia and no false lobulation in normal group;while in the model group, the construction of the normal hepatic lobufe was broken, and the liver was separated bythe fibrous bands into false lobulation, and inflammatory cell infiltration could be seen around the area of convergingpipes, the liver antrum and central vein; as to the treatment group, the hydropic degeneration of liver cell wasobviously alleviated, and there was a little amount ofhyperplastic fiber. Data also showed that theproliferation of spleen T and B lymphocyte was higherin the liver cirrhosis group than that in the control group(P<0.05), and down-regulated after treatment(P<0.05); the expression of Foxp3 m RNA was lower in the livercirrhosis group than that in the normal control(P<0.05), and up-regulated in treatment group(P<0.05); the level ofCD4~+CD25~+Foxp3~+Treg cell was lower in the liver cirrhosis group than that in the normal control(P<0.05), andup-regulated in treatment group(P<0.05). In conclusion, the mechanism of bone marrow mesenchymal stem celltherapy to liver cirrhosis rats maybe relate to inhibiting the abnormal proliferation of lymphocyte and promoting thelevel of Foxp3 mRNA and CD4~+CD25~+Foxp3~+Treg cell. And the early treatment is more effectively.
【Key words】 Bone marrow mesenchymal stem cells; Liver cirrhosis; Lymphocyte proliferation; Regulatory T cells;
- 【文献出处】 免疫学杂志 ,Immunological Journal , 编辑部邮箱 ,2017年07期
- 【分类号】R-332;R575.2
- 【被引频次】7
- 【下载频次】194