常山酮对树突状细胞成熟的影响及其在大鼠同种异体心脏移植免疫耐受中的作用

Effects of halofuginone on maturation of dendritic cells and immune tolerance during homograft heart transplantation of rats

目的观察常山酮对树突状细胞(dendritic cells,DC)成熟的影响,及其在大鼠同种异体心脏移植中的免疫耐受作用,以期进一步了解常山酮的免疫调节作用,为移植免疫耐受提供新的方法和手段并探讨其可能的机制。方法培养大鼠骨髓来源的树突状细胞,通过流式细胞术观察HF对LPS刺激诱导的树突状细胞成熟的影响;建立大鼠心脏移植模型,通过病理切片分析以及混合淋巴细胞反应观察常山酮刺激后的树突状细胞对其免疫耐受的影响。结果流式检测结果表明:对照组细胞表面CD80、CD86、OX62抗原的表达量不高;应用LPS刺激24h之后,CD80、CD86、OX62的表达量明显增加;常山酮和LPS共同刺激24h之后,CD80、CD86、OX62的表达量低于空白组,说明常山酮具有抑制LPS诱导的树突状细胞成熟的能力。在大鼠心脏移植模型中,常山酮刺激的树突状细胞注射入受体大鼠体内后,受体大鼠的移植排斥明显降低,说明常山酮刺激后的树突状细胞可能作为一种新的细胞治疗手段用于治疗移植排斥。结论常山酮可抑制大鼠骨髓来源树突状细胞的成熟;常山酮刺激的树突状细胞诱导免疫排斥的能力下降,常山酮刺激后的树突状细胞具有抑制淋巴细胞增殖的能力。

Objective To explore the role of halofuginone in immune regulation,observe the effects of halofuginone on maturation of dendritic cells and immune tolerance during homograft heart transplantation of rats,in order to provide new ways and means to treat transplantation tolerance and to explore its possible mechanism.Methods Rat bone marrow derived dendritic cells were isolated and the effects of halofuginone in LPS-treated DCs were investigated by flow cytometry;heart transplantation model of rats were established and the effect of halofuginone stimulated dendritic cells in the immune tolerance by pathological analysis and mixed lymphocyte reaction were observed.Results Flow cytometry results show that the expression of cell surface CD80 CD86,OX62 antigens were not high in control group,their expression increased significantly when stimulated by LPS for 24h,and decreased when stimulated by both Changshan ketone and LPS for 24h,and even lower than their expression levels in blank group,which showed that Changshan ketone has the ability to inhibit the maturation of dendritic cells induced by LPS.In rat heart transplantation model,dendritic cells stimulated with Changshan were injected into recipient rats in vivo,and receptor of rat transplantation rejection decreased significantly,which showed that dendritic cells stimulated with Changshan ketone may be used as a new method for cell therapy in treatment of transplant rejection.Conclusion This study systematically observes that halofuginone can inhibit the maturation of rat bone marrow-derived dendritic cells and lymphocyte proliferation for the first time in vivo and in vitro.