Multiple organ failure and macrophage function in severe liver injury: Toll-like receptor and endotoxin clearance
严重肝损伤时的多器官衰竭和巨噬细胞功能:Toll 样受体和内毒素清除
基本信息
- 批准号:15590678
- 负责人:
- 金额:$ 1.47万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:2003
- 资助国家:日本
- 起止时间:2003 至 2005
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Role of innate immunity in the progression of liver injury was investigated in various experimental models of rats.Firstly, Acute hepatic failure (AHF) was induced in rats by injection of D-galactosamine (GalN, 1g/kg b.w.). In this model, the expression of Toll-like receptor (TLR) 4 mRNA of Kupffer cells was increased compared with controls but those of splenic macrophages and alveolar macrophages did not change. The expressions of liver TNF-α mRNA and TLR4 mRNA were increased in parallel with the progression of liver injury.Secondly, AHF with multiple organ failure was induced in rats by the concomitant administration of GalN (500mg/kg b.w.) and endotoxin (LPS; E.coli 055:B55,50μg/kg b.w.). In this model, more than 90% animals died of AHF within 24 hrs after the injection of GalN and LPS. The expression of liver TNF-α mRNA and CD14 mRNA were increased in parallel with the progression of liver injury. However, TLR4 mRNA was down-regulated at first (at 1lhr and 3hr) and recovered later (at 24hr) in survivors. TLR4 antagonist E5564 revealed rescue effect on this lethal AHF model.Thirdly, the expressions of liver TNF-α mRNA, CD14 mRNA and TLR4 mRNA were gradually increased with the progression of inflammation and fibrosis in non-alcoholic steatohepatitis (NASH) of rat induced by choline-deficient 1-amino acid-defined (CDAA) diet. This suggests that gut-derived endotoxin may activate TLR4-TNF-α axis and induce liver injury in this NASH model.In conclusion, activated innate immunity through TLR4 may be important in the development and progression of AHF and NASH.
本研究采用多种动物实验模型,观察天然免疫在肝损伤中的作用。首先,用D-氨基半乳糖(GalN,1g/kg b.w.)与对照组相比,模型组枯否细胞Toll样受体(TLR)4 mRNA表达明显增加,而脾巨噬细胞和肺泡巨噬细胞TLR 4 mRNA表达无明显变化。(2)用GalN(500 mg/kg b.w.)诱导大鼠急性心力衰竭(AHF)伴多器官功能衰竭(MODS)模型。和内毒素(LPS;大肠杆菌055:B55,50μg/kg b.w.)。在该模型中,超过90%的动物在注射GalN和LPS后24小时内死于AHF。肝组织TNF-α mRNA和CD 14 mRNA的表达随肝损伤程度的加重而增加。而在存活者中,TLR 4 mRNA首先下调(在11小时和3小时),随后恢复(在24小时)。TLR 4拮抗剂E5564对该致死性AHF模型有一定的挽救作用。第三,在胆碱缺乏1-氨基酸限定(CDAA)饮食诱导的非酒精性脂肪性肝炎(NASH)大鼠模型中,随着炎症和纤维化的进展,肝脏TNF-α mRNA、CD 14 mRNA和TLR 4 mRNA的表达逐渐增加。提示肠源性内毒素可能通过激活TLR 4-TNF-α轴而导致NASH肝损伤,提示TLR 4介导的天然免疫激活可能在AHF和NASH的发生发展中起重要作用。
项目成果
期刊论文数量(18)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
【アルコールによる臓器障害と線維化】アルコール性肝障害と多臓器不全におけるエンドトキシン,サイトカインおよびマクロファージの意義
【酒精引起的器官损伤和纤维化】内毒素、细胞因子和巨噬细胞在酒精性肝损伤和多器官衰竭中的意义
- DOI:
- 发表时间:2004
- 期刊:
- 影响因子:0
- 作者:Koido S;Hara E;Homma S;Torii A;Toyama Y;Kawahara H;Watanabe M;Yanaga K;Fujise K;Tajiri H;Gong J;Toda G.;福井 博
- 通讯作者:福井 博
中谷吉宏, 福井 博, 他: "急性アルコール投与ラットにおける各種マクロファージのTNF-α産生能におよぼすEP4受容体アゴニストの影響"アルコールと医学生物学. 23. 98-104 (2003)
Yoshihiro Nakatani、Hiroshi Fukui 等人:“EP4 受体激动剂对急性酒精给药大鼠中各种巨噬细胞产生 TNF-α 能力的影响”《酒精与医学生物学》23. 98-104 (2003)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Relation of endotoxin, endotoxin binding proteins and macrophages to severe alcoholic liver injury and multiple organ failure
- DOI:10.1097/01.alc.0000189278.30237.e9
- 发表时间:2005-11-01
- 期刊:
- 影响因子:3.2
- 作者:Fukui, H
- 通讯作者:Fukui, H
Endotoxin clearance and its relation to hepatic and renal disturbances in rats with liver cirrhosis
- DOI:10.1034/j.1600-0676.2001.210110.x
- 发表时间:2001-02-01
- 期刊:
- 影响因子:0
- 作者:Nakatani, Y;Fukui, H;Tsujii, T
- 通讯作者:Tsujii, T
The production of tumor necrosis factor-alpha by macrophages in rats with acute alcohol loading
急性酒精负荷大鼠巨噬细胞产生肿瘤坏死因子-α
- DOI:
- 发表时间:2003
- 期刊:
- 影响因子:0
- 作者:Kitazawa T;Fukui H.et al.
- 通讯作者:Fukui H.et al.
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FUKUI Hiroshi其他文献
FUKUI Hiroshi的其他文献
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{{ truncateString('FUKUI Hiroshi', 18)}}的其他基金
Single crystal elasticity of iron-bearing bridgmanite under lower-mantle conditions by the inelastic x-ray scattering method
非弹性X射线散射法研究下地幔条件下含铁桥锰矿的单晶弹性
- 批准号:
19H02004 - 财政年份:2019
- 资助金额:
$ 1.47万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Determination of elastic wave velocities of iron-bearing magnesium silicate under lower mantle pressure conditions by means of inelastic X-ray scattering
非弹性X射线散射测定低地幔压力条件下含铁硅酸镁的弹性波速
- 批准号:
19740327 - 财政年份:2007
- 资助金额:
$ 1.47万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
マクロファージと肝障害:Toll-like受容体制御による新規治療の探索
巨噬细胞和肝损伤:通过Toll样受体调节寻找新的治疗方法
- 批准号:
19590784 - 财政年份:2007
- 资助金额:
$ 1.47万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Emndotoxin binding proteins and endotoxin-mediated macrophage reaction : Prospect for future treatment of liver cirrhosis
内毒素结合蛋白和内毒素介导的巨噬细胞反应:肝硬化未来治疗的展望
- 批准号:
11670527 - 财政年份:1999
- 资助金额:
$ 1.47万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
BIOORGANIC STUDIES ON BIOFUNCTIONAL COMPONENTS IN VEGETABLES FOR CHEMICAL BREEDING
化学育种蔬菜中生物功能成分的生物有机研究
- 批准号:
11660113 - 财政年份:1999
- 资助金额:
$ 1.47万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Macrophage functions in severe liver disturbance and multiple organ failure
巨噬细胞在严重肝功能紊乱和多器官衰竭中的功能
- 批准号:
08670612 - 财政年份:1996
- 资助金额:
$ 1.47万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Chemical and biofunctional analysis for chemical breeding of vegetables
蔬菜化学育种的化学和生物功能分析
- 批准号:
08660138 - 财政年份:1996
- 资助金额:
$ 1.47万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Endotoxin inactivation by endotoxin binding proteins : Significance in severe liver disturbances
内毒素结合蛋白灭活内毒素:在严重肝脏疾病中的意义
- 批准号:
06670578 - 财政年份:1994
- 资助金额:
$ 1.47万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
How does a plant express its secondary metabolism in the special tissues?
植物如何在特殊组织中表达其次生代谢?
- 批准号:
05660120 - 财政年份:1993
- 资助金额:
$ 1.47万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
Endogenous Inducer of secondary Metabolism in Lithospermum erythrorhizon Cell Cultures
紫草细胞培养物次生代谢的内源诱导剂
- 批准号:
03670998 - 财政年份:1991
- 资助金额:
$ 1.47万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
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