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Synthesis of Toll-like receptor 4 in Kupffer cells and its role in alcohol-induced liver disease

摘要Objectives To observe the synthesis of Toll-like receptor (TLR) 4 protein and its mRNA expression in Kupffer cells (KCs) and evaluate the role of TLR 4 in liver injury to rats through alcohol-induced liver disease.Methods Twenty-eight Wistar rats were divided into two groups: ethanol-fed (group E) and control (group C). Group E rats were given ethanol at a dose of 5-12 g@kg-1@d -1, while group C received dextrose. Animals from bot h groups were killed at 4 and 8 weeks. The KCs were isolated and synthesis of T LR 4 protein was determined by laser scanning confocal microscopy. TLR 4 mRNA e xpression in KCs was determined by reverse transcription polymerase chain reacti on (RT-PCR) analysis. The levels of endotoxin, tumor necrosis factor-α (TN F-α) and interleukin-6 (IL-6) in plasma were determined. Changes in liver pathology were observed.Results Laser scanning confocal microscopy showed that the intensity of fluorescence of TLR 4 protein in group E was stronger than group C. Ethanol administration led to a significant increase in TLR 4 mRNA expression in group E compared with grou p C (P<0.05). The concentrations of plasma endotoxin, TNF-α and IL- 6 were higher in group E than in group C (P<0.05). Liver sections from rat s in group E demonstrated marked pathological changes.Conclusion Ethanol administration can lead to the synthesis of TLR 4 protein and its gene expression in KCs, indicating that TLR 4 may play a major role in the development of alcohol-induced liver injury.

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作者 左国庆 [1] 龚建平 [2] 刘长安 [2] 吴传新 [2] 李生伟 [2] 戴立里 [1] 学术成果认领
作者单位 Department of Digestive Disease, The Second College of Clinical Medicine and The Second Affiliated Hospital of Chongqing University of Medical Sciences, Chongqing 400010, China [1] Department of General Surgery, The Second College of Clinical Medicine and The Second Affiliated Hospital of Chongqing University of Medical Sciences, Chongqing 400010, China [2]
分类号 R57
栏目名称 ORIGINAL ARTICLES
发布时间 2004-01-08
基金项目
国家自然科学基金
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中华医学杂志(英文版)

中华医学杂志(英文版)

2003年116卷2期

297-300页

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