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慢加亚急性肝衰竭大鼠肠源性内毒素血症时Th17/Treg表达变化的实验研究
谭年花,陈 斌
0
(湖南中医药大学,湖南 长沙,410208;湖南中医药大学第一附属医院,湖南 长沙,410007)
摘要:
目的:观察Treg/Th17细胞失衡及相关细胞因子在慢加亚急性肝衰竭肠源性内毒素血症(IETM)时的表达变化,进而探讨Treg/Th17细胞对内毒素介导的炎症反应的调控作用。方法:采用牛血清白蛋白致敏建立免疫性肝纤维化大鼠模型,以腹腔注射D-Gal+LPS液(合D-Gal 400mg/kg,LPS 100μg/kg)急性攻击建立肝衰竭IETM大鼠模型。流式细胞术检测不同时间点大鼠外周血中Th17、Treg细胞频数,ELISA法测定不同时间节点大鼠结肠组织IL-10、TNF-α、IL-17A、IL-23、TGF-β水平。结果:与正常组比较,模型组Treg、Th17细胞频数在各时间节点均升高(P<0.05),Treg、Th17细胞与前一时间节点比较均有上升(P<0.05);与正常组比较,模型组结肠组织Treg/Th17型细胞因子IL-17A、IL-23、TNF-α、TGF-β、IL-10各时间节点表达均升高(P<0.05),且各炎症因子与前一时间节点比较均有上升(P<0.05);正常组大鼠IL-10、TGF-β等抑炎因子水平高于IL-17A、IL-23、TNF-α等促炎因子,模型组Th17比例高于Treg,失衡向Th17方向偏移。结论:肝衰竭IETM发生时Treg/Th17细胞失衡,向Th17方向偏移,相关抑炎、促炎因子均释放增加,加剧IETM程度。
关键词:  慢加亚急性肝衰竭  肠源性内毒素血症  Treg细胞  Th17细胞  实验研究
DOI:
Change in the expression of T helper 17 cells/regulatory T cells at the time of intestinal endotoxemia in rats with subacute-on-chronic liver failure:An experimental study
TAN Nianhua,CHEN Bin
(Hunan University of Chinese Medicine,Changsha 410208,Hunan,China;The First Affiliated Hospital of Hunan University of Chinese Medicine,Changsha 410007,Hunan,China)
Abstract:
Objective:To investigate T helper 17 cell(Th17)/regulatory T cell(Treg)imbalance and the change in related cytokines at the time of intestinal endotoxemia(IETM)in subacute-on-chronic liver failure,as well as the regulatory effect of Th17/Treg cells on endotoxin-mediated inflammation response.Methods:Bovine serum albumin sensitization was used to establish a rat model of immune liver fibrosis,and intraperitoneal injection of D-Gal+LPS solution(containing D-Gal 400mg/kg and LPS 100 μg/kg)was used for acute attack to establish a rat model of IETM and liver failure.Flow cytometry was used to measure the frequencies of Th17 and Treg cells in peripheral blood at different time points,and ELISA was used to measure the levels of interleukin-10(IL-10),tumor necrosis factor-α(TNF-α),interleukin-17A(IL-17A),ilterleukin-23(IL-23),and transforming growth factor-β(TGF-β)in colon tissue at different time points.Results:Compared with the normal group,the model group had significant increases in the frequencies of Th17 and Treg cells at each time point(P<0.05),with significant increases from the former to the latter time point(P<0.05).Compared with the normal group,the model group had significant increases in the levels of IL-17A,IL-23,TNF-α,TGF-β,and IL-10 in colon tissue at each time point(P<0.05),with significant increases from the former to the latter time point(P<0.05).In the normal group,the levels of the inflammatory cytokines IL-10 and TGF-β were higher than those of the proinflammatory factors IL-17A,IL-23,and TNF-α,while in the model group,the percentage of Th17 cells was higher than that of Treg cells.Conclusion:Treg/Th17 imbalance is observed at the time of IETM in liver failure,and the percentage of Th17 cells is higher than that of Treg cells.There are significant increases in the release of related anti-inflammatory and proinflammatory factors,which causes the aggravation of IETM.
Key words:  subacute-on-chronic liver failure  intestinal endotoxemia  regulatory T cell  T helper 17 cell  experimental study

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