Induction of acute hepatic injury by endotoxin in mice

来源 :Hepatobiliary & Pancreatic Diseases International | 被引量 : 0次 | 上传用户:yufan123456789
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Objective: To investigate the changes of scavenger re-ceptor (SR) and CD_(14) in Kupffer cells in endotox-emia in order to uncover the mechanism of the liverto turn a defense organ into effector one in sepsis.Methods: Mouse models of endotoxemia of differentseverity were reproduced by injection of different do-ses of lipopolysaccharide (LPS) via the tail vein.The expression of SR and CD_(14) in the liver was as-sayed by immunohistochemistry and was subsequent-ly analyzed with an image analysis system. The levelsof TNF-α and IL-6 in liver tissue were determinedwith ELISA.Results: The expression of SR in the liver in the high-dose group was markedly decreased one hour afterinjection of LPS, and also in the low-dose group at 3hours. The expression of SR in the liver in the twogroups was shown to be progressively decreased withthe time prolonged. There was significant differencein average optical density (OD) values of SR be-tween the two groups. The expression of CD_(14) in thetwo groups was shown to be significantly increasedone hour after injection of LPS, and more signifi-cantly with the time prolonged. But there was no sig-nificant difference in OD values of CD_(14) between thetwo groups. The contents of intrahepatic proinflam-matory mediators TNF-α, IL-6, ALT and TBILwere significantly increased after injection of LPS.Correlation analysis revealed that the changes ofTNF-α, IL-6, ALT, and TBIL were negatively cor-related with the expression of SR, and positively withthe expression of CD_(14).Conclusion: The up-regnlation of CD_(14) expressionand down-regulation of SR expression on Kupffercells might be one of the important mechanisms forthe conversion of Kupffer cells from immune defen-sive to inflammatory response cells in acute hepaticinjury. Objective: To investigate the changes of scavenger re-ceptor (SR) and CD_ (14) in Kupffer cells in endotox-emia in order to uncover the mechanism of the liverto turn a defense organ into effector one in sepsis. Methods: Mouse models of endotoxemia of different severity reproduced by injection of different do-ses of lipopolysaccharide (LPS) via the tail vein. The expression of SR and CD 14 in the liver was as-sayed by immunohistochemistry and was subsequently-ly analyzed with an image analysis system. The levels of TNF-α and IL-6 in liver tissue were determined with ELISA. Results: The expression of SR in the liver in the high-dose group was markedly decreased one hour after injection of LPS, and also in the low-dose group The expression of SR in the liver in the twogroups was shown to be progressively decreased decreased with the time prolonged. There was significant difference in the average optical density (OD) values ​​of SR be-tween the two groups. The expression of CD_ (14) in thetwo groups was showed significantly increasedone hour after injection of LPS, and more signifi-cantly with the time prolonged. But there was no sig-nificant difference in OD values ​​of CD_ (14) between thetwo groups. The contents of intrahepatic proinflam-matory mediators TNF-α, IL-6, ALT and TBILwere significantly increased after after injection of LPS. Correlation analysis revealed that the changes of TNF-α, IL-6, ALT, and TBIL were negatively cor- related with the expression of SR, and positively withthe Expression of CD_ (14). Conflusion: The up-regnlation of CD_ (14) expression and down-regulation of SR expression on Kupffer cells might be one of the important mechanisms forthe conversion of Kupffer cells from immune defen-sive to inflammatory response cells in acute hepaticinjury.
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