文章摘要
山奈酚通过增强Treg细胞免疫抑制功能延长移植物生存时间
Kaempferol prolongs the graft survival time by enhancing the immunosuppressive function of Treg cells
投稿时间:2019-03-04  修订日期:2019-03-08
DOI:
中文关键词: 
英文关键词: kaempferol  Treg  Foxp3
基金项目:
作者单位E-mail
葛茹茹 上海交通大学附属第一人民医院 上海 200080 中国 milannice@sjtu.edu.cn 
徐辰鸣 上海交通大学附属第一人民医院 上海 200080 中国  
顾蔚 上海交通大学附属第一人民医院 上海 200080 中国  
程自豪 上海交通大学附属第一人民医院 上海 200080 中国  
葛骥夫 上海交通大学附属第一人民医院 上海 200080 中国  
秦燕 上海交通大学附属第一人民医院 上海 200080 中国  
邱建新 上海交通大学附属第一人民医院 上海 200080 中国 jasonqiu@sjtu.edu.cn 
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中文摘要:
      目的 探讨应用山萘酚增强Treg细胞免疫抑制功能,从而抑制大鼠移植物排斥反应并改善移植物生存的作用和机制。方法:以Wister大鼠和SD大鼠分别为供、受体,建立同种异体皮肤移植排斥反应动物模型。将受体SD大鼠分为3组,对照组I(自体移植大鼠),对照组II(移植后即不予任何药物的受体大鼠),治疗组(予山萘酚一日50mg/KG)。记录并观察受体老鼠皮肤移植物的情况,记录移植物失功时间(移植物皮片80%面积发生排斥)。流式细胞术(FACS)分别检测治疗组及两个对照组处理7天后脾细胞、淋巴细胞CD4+CD25+调节性T细胞中FOXP3和CTLA-4的蛋白水平,RT-PCR检测移植7天后脾细胞、淋巴细胞FOXP3、CTLA-4和IL-10的mRNA水平,并采用HE染色组织病理学观察术后7天移植皮片的病理表现,淋巴细胞浸润程度。体外实验T细胞增殖抑制试验(CD3/CD28抗体诱导T细胞成熟,加入Treg观察抑制T细胞情况),同时加入山萘酚作为对照,观察Treg功能情况。结果:1.山萘酚能增强移植后同种异体移植物的生存时间(DMSO组6.3±0.3天 VS. 山萘酚组13.7±0.39天)(P<0.01),减少移植物中淋巴细胞的浸润;2.RT-PCR显示山萘酚可增强细胞CTLA-4、FOXP3和IL-10的mRNA水平(2-Ct值,CTLA-4对照组9.24±0.17 VS. 山萘酚组12.48±0.14,P<0.05,FOXP3对照组 0.96±0.07 VS. 山萘酚组1.41±0.07,P<0.01,IL-10对照组 0.95±0.12 VS. 山萘酚组1.50±0.16,P<0.05);3.体外T细胞增殖抑制实验中,山萘酚可显著增强Treg细胞的免疫抑制功能。结论:山萘酚在大鼠皮肤移植模型中可显著延长皮片移植物的生存时间,并同时使Treg细胞相关的下游细胞因子IL-10、转录因子FOXP3、表面分子CTLA-4的蛋白和RNA水平显著提升,并在体外T细胞增殖抑制实验中也得到了证实,表明山萘酚可以显著提升Treg细胞的免疫抑制功能,在提高移植物的生存方面有一定的价值。
英文摘要:
      Objective:To discuss effects and mechanism on promoting survival time of allograft by intraperitoneal injection of kaempferol for the rats that accept skin transplantation. Methods: Wister rats and SD rats were used as donores and receptors to establish the animal models of allograft skin transplantation rejection. According to the different using of medicine, the rats were divided into three groups, control group I (autologous transplant rats), control group II (receptor rats which were not taken any drugs after transplantation) and treatment group (receptor rats which were taken kaempferol with a dose of 50 mg/kg per day after transplantation). The skin grafts of receptors rat were observed and recorded, the expiration time (80% graft rejection) was also recorded. Flow cytometry respectively detected the protein level of the FOXP3,CTLA-4 and IL-10 in the receptor spleen lymphocyte in the three groups 7 days after transplantation. We observed the pathological manifestation and lymphocyte infiltration of postoperative skin grafts which were dyed by HE method. The T cell proliferation inhibition test in vitro (CD3 / CD28 antibody induced T cells mature, which was added into Treg cell to observe the situation of weak T cells), added kaempferol as a control at the same time, observed the function of Treg cell.Results:1.kaempferol can effectively prolong the survival time of allograft. (DMSO group 6.3±0.3days VS. kaempferol group 13.7±0.39days)(P<0.01),and decrease infiltration of lymphocyte in the tissue of allgrafts.2.RT-PCR shows that kaempferol could increase the intracellular mRNA level of CTLA-4,FOXP3 and IL-10.(2-△Ct,CTLA-4 control group 9.24±0.17 VS. kaempferol group 12.48±0.14,P<0.05,Foxp3 control group 0.96±0.07 VS. kaempferol group 1.41±0.07,P<0.01,IL-10 control group 0.95±0.12 VS. 1.50±0.16,P<0.05).3.Kaempferol enhances the suppressive function of Treg cells in vitro. Conclusions: kaempferol can effectively prolong the survival time of the allograft in the rat skin transplantation model, and upregulate protein and mRNA level of Treg cell relevant molecule IL-10,transcription factor Foxp3,surface molecule CTLA-4.Then the result is also proved in suppression assay of T cell in vitro which shows value of kaempferol in enhancing function of Treg cell so as to prolong survival time of the allograft.
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