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10d;耐受组(10只),术后存活100d,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
Objective To investigate the relationship between immune tolerance and the changes of helper T cell (Th), regulatory T cell (Treg) cytokines, related signaling pathway proteins during immune tolerance process in rat models of liver transplantation. Methods The orthotopic liver transplantation rat models were established by double-cuff technique. All rats were divided into 3 groups. In the operative control group (n=6), sham operation was performed without liver transplantation. In the short-term group (n=10), the rats survived for 10 d after liver transplantation. In the immune tolerance group (n=10), the rats survived for 100 d after operation and the function of the transplanted liver was restored to normal. The expression levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), Th1 cytokines [interferon (IFN)-γ, interleukin (IL)-2 and tumor necrosis factor (TNF)-α], Th2 cytokines (IL-4, IL-5, IL-6 and IL-13), Th17 cytokines [granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-17A], Treg cytokines [IL-10, transforming growth factor (TGF)-β and IL-12p] were quantitatively measured. The serum sample of rats in each group was detected by protein chip analysis. Results Compared with the operative control group, the AST level in the short-term group was significantly down-regulated, whereas the ALT level was significantly up-regulated (both P<0.05). However, the AST and ALT levels did not significantly differ between the immune tolerance group and operative control group (both P>0.05). In the liver tissues of rats in each group, the expression levels of Th1 cytokines IFN-γ and IL-2 in the shortterm group were significantly higher than those in the operative control group (both P<0.05). The expression level of Th2 cytokine IL-4 in the immune tolerance group was significantly lower than that in the operative control group (P<0.05). The expression levels of Th2 cytokines IL-5, IL-6 and IL-13 in the short-term group were significantly lower than those in the operative control group (a
作者
李先亮
白纯
杨龙
李瀚
吕少诚
朱继巧
马军
寇建涛
贺强
Li Xianliang;Bai Chun;Yang Long;Li Han;Lyu Shaocheng;Zhu Jiqiao;Ma Jun;Kou Jiantao;He Qiang(Department of Hepatobiliary,Pancreatic and Splenic Surgery,Beijing Chaoyang Hospital,Capital Medical University,Beijing 100020,China)
出处
《器官移植》
CAS
CSCD
北大核心
2019年第4期416-422,共7页
Organ Transplantation
基金
国家自然科学基金(81571554、81471590、81273270)
关键词
肝移植
免疫耐受
辅助性T细胞
调节性细胞
信号通路蛋白
Liver transplantation
Immune tolerance
Helper T cell
Regulatory T cell
Signaling pathway protein
