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[胆汁淤积性胆汁酸对大鼠肝内胆管细胞的毒性作用]

[Toxicity of cholestatic bile acids on intrahepatic biliary cells of the rat].

作者信息

Diallo A, Dumont M, Faye B, Poirel O, Erlinger S

机构信息

Laboratoire de Pharmacologie et Physiologie-UCAD.

出版信息

Dakar Med. 1994;39(1):99-107.

PMID:7493531
Abstract

The aim of this study is: 1. to isolate intrahepatic biliary epithelial cells and, 2. to study the toxicity of cholestatic biliary acids on these cells. Cells were isolated from rats with proliferated bile duct-cells, that were induced by a 21 days bile duct ligation. They were characterized by glutamyltranspeptidase and cytokeratins 7 and 19 using histochemical or immuno cytochemical methods. Isolated cells were incubated with different concentrations (250, 500, 1000 and 2000 microM) of cholestatic biliary acids, lithocholate sulfate (LCS) and taurolithocholate sulfate (TLCS. Cells viability is estimated by three methods: Trypan blue, LDH release and MTT test. We obtained purified fractions of non parenchymal liver cells enriched in biliary epithelial cells (> 95%). On these cells, we showed toxicity of LCS and TLCS and determined CI 10 and CI 50 of these acids which were respectively 800 microM and 2 mM for LCS; 1.4 and 2 mM for TLCS. These results indicate that cholestatic biliary acids (LCS and TLCS) are toxic for biliary cells. This cytotoxicity can be probably a possible mechanism of cholestasis.

摘要

本研究的目的是

  1. 分离肝内胆管上皮细胞;2. 研究胆汁淤积性胆汁酸对这些细胞的毒性。细胞从经21天胆管结扎诱导胆管细胞增殖的大鼠中分离得到。使用组织化学或免疫细胞化学方法,通过谷氨酰转肽酶、细胞角蛋白7和19对其进行鉴定。将分离的细胞与不同浓度(250、500、1000和2000微摩尔)的胆汁淤积性胆汁酸、硫酸石胆酸(LCS)和牛磺熊去氧胆酸(TLCS)一起孵育。通过三种方法评估细胞活力:台盼蓝、乳酸脱氢酶释放和MTT试验。我们获得了富含胆管上皮细胞(>95%)的非实质肝细胞纯化组分。在这些细胞上,我们显示了LCS和TLCS的毒性,并确定了这些酸的半数抑制浓度(CI)10和CI50,LCS分别为800微摩尔和2毫摩尔;TLCS分别为1.4和2毫摩尔。这些结果表明胆汁淤积性胆汁酸(LCS和TLCS)对胆管细胞有毒性。这种细胞毒性可能是胆汁淤积的一种可能机制。

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