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大鼠肝移植免疫耐受过程Th细胞和Treg细胞因子及信号通路蛋白的变化研究

李先亮 白纯 杨龙 李瀚 吕少诚 朱继巧 马军 寇建涛 贺强

李先亮, 白纯, 杨龙, 等. 大鼠肝移植免疫耐受过程Th细胞和Treg细胞因子及信号通路蛋白的变化研究[J]. 器官移植, 2019, 10(4): 416-422. doi: 10.3969/j.issn.1674-7445.2019.04.011
引用本文: 李先亮, 白纯, 杨龙, 等. 大鼠肝移植免疫耐受过程Th细胞和Treg细胞因子及信号通路蛋白的变化研究[J]. 器官移植, 2019, 10(4): 416-422. doi: 10.3969/j.issn.1674-7445.2019.04.011
Li Xianliang, Bai Chun, Yang Long, et al. Changes of Th, Treg cytokines and signaling pathway proteins during immune tolerance process in rat models of liver transplantation[J]. ORGAN TRANSPLANTATION, 2019, 10(4): 416-422. doi: 10.3969/j.issn.1674-7445.2019.04.011
Citation: Li Xianliang, Bai Chun, Yang Long, et al. Changes of Th, Treg cytokines and signaling pathway proteins during immune tolerance process in rat models of liver transplantation[J]. ORGAN TRANSPLANTATION, 2019, 10(4): 416-422. doi: 10.3969/j.issn.1674-7445.2019.04.011

大鼠肝移植免疫耐受过程Th细胞和Treg细胞因子及信号通路蛋白的变化研究

doi: 10.3969/j.issn.1674-7445.2019.04.011
基金项目: 

国家自然科学基金 81571554

国家自然科学基金 81471590

国家自然科学基金 81273270

详细信息
    通讯作者:

    李先亮,男,1971年生,博士,副主任医师,研究方向为器官移植诱导免疫耐受,Email:lixianliangbjcy@126.com

  • 中图分类号: R617, R322.1+1

Changes of Th, Treg cytokines and signaling pathway proteins during immune tolerance process in rat models of liver transplantation

More Information
  • 摘要:   目的  探讨大鼠肝移植免疫耐受过程中,辅助性T细胞(Th)和调节性T细胞(Treg)细胞因子及相关信号通路蛋白的变化与免疫耐受的关系。  方法  双袖套法建立原位肝移植模型,将大鼠分为3组:手术对照组(6只),假手术不进行肝移植;短期组(10只),术后存活10 d;耐受组(10只),术后存活100 d,移植肝功能恢复正常。检测各组大鼠肝功能指标如丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST),Th1细胞因子[干扰素(IFN)-γ、白细胞介素(IL)-2、肿瘤坏死因子(TNF)-α],Th2细胞因子(IL-4、IL-5、IL-6、IL-13),Th17细胞因子[粒细胞-巨噬细胞集落刺激因子(GM-CSF)、IL-17A],Treg细胞因子[IL-10、转化生长因子(TGF)-β、IL-12p]表达水平。对各组大鼠血清进行蛋白芯片检测。  结果  与手术对照组比较,短期组AST明显降低,ALT明显升高(P < 0.05)。而耐受组与手术对照组的AST、ALT水平比较,差异均无统计学意义(均为P > 0.05)。各组大鼠的肝组织中,与手术对照组比较,短期组Th1细胞因子IFN-γ、IL-2表达水平明显升高(均为P < 0.05);耐受组Th2细胞因子IL-4的表达水平明显低于手术对照组(P < 0.05);短期组Th2细胞因子IL-5、IL-6、IL-13的表达水平明显低于手术对照组(P < 0.05);耐受组IL-17A的表达水平明显高于手术对照组(P < 0.05)。耐受组IL-10、IL-12p的表达水平明显高于手术对照组(均为P < 0.05),短期组TGF-β的表达水平明显高于手术对照组(P < 0.05)。与手术对照组比较,短期组细胞间黏附分子(ICAM)-1、前血小板碱性蛋白(Ppbp)、神经纤毛蛋白(Neuropilin)-2、Notch-2蛋白的表达水平明显升高(均为P < 0.05);耐受组趋化因子配基17(CXCL17)、ICAM-1、Neuropilin-2蛋白的表达水平明显升高(均为P < 0.05),而B7-1蛋白的表达水平显著减低(P < 0.05)。  结论  在大鼠肝移植自然免疫耐受过程中,Treg类细胞因子(IL-10、TGF-β、IL-12p),IL-6,IL-17以及细胞表面的跨膜信号通路分子(ICAM-1、Neuropilin-2、B7-1蛋白)在其中起到了重要的作用。

     

  • 图  1  各组大鼠的肝功能比较

    与手术对照组比较,aP < 0.05

    Figure  1.  Comparison of liver function in rats among each group

    图  2  各组大鼠肝组织细胞因子表达水平的比较

    与手术对照组比较,aP < 0.05

    Figure  2.  Comparision of cytokine expression levels of liver tissues in rats among each group

    图  3  各组大鼠血清细胞因子表达水平的比较

    Figure  3.  Comparision of serum cytokine expression levels in rats among each group

    图  4  各组大鼠的蛋白芯片分析

    A图为手术对照组和短期组的基因差异分析;B图为手术对照组和耐受组的基因差异分析;C图为手术对照组和短期组的GO生物过程分析;D图为手术对照组和耐受组的GO生物过程分析;E图为手术对照组和短期组的GO分子功能分析;F图为手术对照组和耐受组的GO分子功能分析

    Figure  4.  Protein microarray analysis in rats among each group

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出版历程
  • 收稿日期:  2019-04-25
  • 网络出版日期:  2021-01-19
  • 刊出日期:  2019-07-15

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