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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。
Objective To investigate the effect of bone marrow mesenchymal stem cell transplantation on the autoimmune function of cirrhotic rats and to provide a theoretical basis for clinical treatment. Methods 150 healthy male Wistar rats were randomly divided into three groups: control group (without any intervention), cirrhosis group (rats with cirrhosis model), treatment group (rats with liver cirrhosis model After giving bone marrow mesenchymal stem cell transplantation treatment). The proliferation of T and B lymphocytes, the level of CD4 ~ + CD25 ~ + Foxp3 ~ + regulatory T cells and the expression of Foxp3 mRNA in spleens of rats in each group were detected. Results In the control group, the hepatocytes were intact with no fibrogenesis and false lobules. The hepatic lobules in the cirrhosis group were damaged, the false lobules were appeared, the hepatocytes were edematous and degenerated, the inflammatory cells infiltrated. The hepatic cells The extent of edema degeneration and necrosis was significantly lower than that of cirrhosis group, but still can see the proliferation of fibrous tissue. The proliferation of splenic T and B lymphocytes in cirrhotic rats was significantly higher than that in control group (P <0.05). After BMSCs treatment, the proliferation of T and B lymphocytes in spleen of rats in treatment group was significantly lower than that in cirrhosis group (P <0.05). The expression of Foxp3 mRNA in spleen in cirrhosis group was significantly lower than that in control group (P <0.05). After BMSCs treatment, Foxp3 mRNA expression in spleen in cirrhosis group was higher than that in cirrhosis group (P <0.05) ; The percentages of CD4 ~ + CD25 ~ + Foxp3 ~ + regulatory T cells in spleen of cirrhosis group were significantly lower than those in normal group (P <0.05). After treatment with BMSCs, the percentage of CD4 ~ + CD25 ~ + regulatory T cells Percentage higher than cirrhosis (P <0.05). Conclusion Bone marrow mesenchymal stem cell transplantation can affect the autoimmune function by inhibiting the proliferation of T and B lymphocytes and increasing the expression of CD4 ~ + CD25 ~ + Foxp3 ~ + regulatory T cells and Foxp3 mRNA in the spleen Return