The alleviative effects of lipopolysaccharide pretreatment on thioacetamide-induced liver injury

• Main Authors: Huan-Nan Chen, 陳奐男
• Other Authors: Ching-Feng Weng
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/23730455741463290475

碩士 === 國立東華大學 === 生物技術研究所 === 92 === Liver injury would be induced by various hepatotoxins including chemicals, toxin, and virus. Thioacetamide (TAA), a hepatotoxin, is a common inducer for studying the liver fibrosis and cirrhosis. In the pathogenesis of liver fibrosis, cytochrome P450 enzymes would be induced to produce oxidative stress.Hepatic stellate cells (HSCs), the key cells in the process of liver fibrosis, will be activated to produce extracellular matrix proteins (ECM) and collagens by several factors such as transforming growth factorβ1 (TGFβ1) and leptin which are secreted increasingly by macrophage cells in liver. Bacterial endotoxin, lipopolysaccharide (LPS), can cause liver inflammation and increases liver injury when is co-treated with TAA. Pretreatment with a low dose of LPS has been shown to protect liver from hepatotoxic causation by decreasing cytochrome P450 enzymes and inflammatory factors. However, the effects of LPS pretreatment in TAA-induced liver fibrosis on the expressions of TGFβ1 and leptin are still not known. In this experiment, SD rats were pretreated intraperitoneally（IP）with LPS (5 mg/kg B.wt) for 24 hours, and then treated with TAA （200 mg/kg B.wt/3 days,IP）for one month. The data showed that TAA caused liver fibrosis with evelation of GOT/GPT in blood, increases of collagen 1 and 3 mRNA, and high expressions of TGFβ1 and leptin. After LPS pretreatment, the expression of collagen 3, TGFβ1 mRNA and leptin protein were decreased. In conclusion, LPS pretreatment could improve the TAA-induced liver fibrosis by decreasing TGFβ1 and leptin.