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应用3,4-DAA介导IDO高表达诱导小鼠皮肤移植免疫负向调节的研究

Negative regulation on allograft immune response induced with up-regulated expression of IDO mediated by3,4-DAA
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摘要 目的探索N-3,4-二甲基氧基肉桂酰一邻氨基苯甲酸(3,4-DAA)通过吲哚胺2,3双加氧酶(IDO)高表达介导小鼠皮肤移植免疫负向调节的作用及其机制。方法建立小鼠皮肤移植模型,收集受鼠脾脏淋巴细胞及血清,检测白细胞介素2(IL-2)和7干扰素(IFN-7)含量;流式细胞仪测定T淋巴细胞各亚群;RT_PCR检测ID0信使RNA(mRNA)基因表达水平。结果3,4-DAA对小鼠脾脏淋巴细胞增殖有显著抑制作用,并呈现剂量效应关系。3,4-DAA可显著抑制小鼠IL-2和IFN-7的产生(P〈0.05)。3,4-DAA处理组CD3+、CD4+、CD8+T淋巴细胞百分率呈现下降趋势,同时调节性T淋巴细胞百分率增加,但差异无统计学意义(P〉0.05)。3,4-DAA处理组ID0mRNA基因表达较对照组均显著增高(P〈0.05)。结论3,4-DAA可抑制T淋巴细胞增殖,并通过上调IDO高表达下调移植物免疫应答反应,显示出免疫负向调节的效应。 Objective To investigate role of N-(30,40-dimethoxycinnamonyl) anthranilic acid (3,4-DAA) in mediating the negative immune regulation by indoleamine 2, 3 dioxygenase in mice skin transplantation. Method The mice skin transplant model was established. T lymphocytes were isolated from mice sptenocytes, and serum was collected. ELISA was applied to detect the IL-2 and IFN-7 concentrations in culture supernates of mice spleen lymphocytes and serum. Flow cytometry was applied to examine the phenotypes of T lymphocytes and RT-PCR to analyze the IDO mRNA transcription. Results T lymphocyte proliferation was significantly decreased by 3, 4-DAA and the concentrations of IL-2 and IFN-7 were apparently decreased in 3,4-DAA group as compared with those in control group. The percentages of CD3 + , CD4+ and CD8 + T lymphocytes were lower, and the percentage of CD4 + CD25 + T lymphocytes was higher in 3,4-DAA disposal group than in control group, but there was no significant difference. IDO mRNA expression showed obvious increase in 3,4- DAA group as compared with control group. Conclusion 3, 4-DAA can up-regulate the IDO expression to induce the increasing metabolism of tryptophan, subsequently inhibiting T cell proliferation and showing specific property of negative immune regulation.
出处 《中华器官移植杂志》 CAS CSCD 北大核心 2013年第10期620-624,共5页 Chinese Journal of Organ Transplantation
基金 上海市科委器官移植重点实验室研究项目(10Dz2212000)
关键词 邻氨基苯甲酸类 双加氧酶类 免疫调节 皮肤移植 小鼠 Anthranilic acids Dioxygenase Immunoregulation Skin transplantatiom Mice
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参考文献10

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