Endotoxin clearance and its relation to hepatic and renal disturbances in rats with liver cirrhosis
Endotoxin clearance and its relation to hepatic and renal disturbances in rats with liver cirrhosis
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DOI：
10.1034/j.1600-0676.2001.210110.x
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发表时间：
2001-02-01
期刊：
影响因子：
--
通讯作者：
Tsujii, T
中科院分区：
文献类型：
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作者：
Nakatani, Y;Fukui, H;Tsujii, T
背景/目的：关于肝硬变时巨噬细胞内毒素清除和细胞因子分泌的研究鲜为人知。本研究旨在探讨不同巨噬细胞清除内毒素和释放肿瘤坏死因子α与肝硬变时肝肾功能损害的关系。方法：雄性SD大鼠灌胃0.04%硫代乙酰胺6个月或12个月。输注[H-3]-内毒素(10µg/kg bw)的脏器分布。测定肝硬变大鼠和对照组大鼠Kupffer细胞、脾巨噬细胞和外周血单核细胞(1×10(4)cell/ml)对[H-3]-内毒素的摄取和肿瘤坏死因子α的分泌。结果：肝硬变大鼠体内内毒素积聚较多，脾肾内积聚较多，与血清总胆红素、天冬氨酸氨基转移酶、丙氨酸氨基转移酶、血尿素氮、肌酐、肿瘤坏死因子α升高有关。肝硬变大鼠Kupffer细胞内毒素摄取和肿瘤坏死因子α释放减少，脾巨噬细胞和外周血单核细胞分泌增加。结论：在肝硬变中，肝外巨噬细胞对内毒素的清除障碍和肿瘤坏死因子-α的分泌增加可能在肝肾功能紊乱的发生发展中起重要作用。
Background/Aims: Little is known about endotoxin clearance and secretion of cytokines from macrophages in liver cirrhosis. The aims of this study were to investigate the relationship of endotoxin clearance and release of tumor necrosis factor alpha by various macrophages to hepatic and renal disturbances in liver cirrhosis. Methods: Male Sprague-Dawley rats were given 0.04% thioacetamide orally for 6 or 12 months. The organ distribution of infused [H-3]-endotoxin (10 mug/kg b.w.) was analyzed at 30 min or at 24 h. Uptake of [H-3]-endotoxin and secretion of tumor necrosis factor alpha by Kupffer cells, splenic macrophages and peripheral blood monocytes (1 X 10(4) cells/ml) from cirrhotic and control rats were determined. Results: In cirrhotic rats, more endotoxin was left in the body and more endotoxin accumulated in the spleen and kidney, and thus was related to elevation of serum total bilirubin, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine and tumor necrosis factor alpha. Endotoxin uptake and tumor necrosis factor alpha release by the Kupffer cells were decreased and those by the splenic macrophages and peripheral blood monocytes were increased in cirrhotic rats. Conclusions: In liver cirrhosis, impaired clearance of endotoxin together with increased secretion of tumor necrosis factor alpha by extrahepatic macrophages may play an important role in the progression of hepatic and renal disturbances.