Down-regulation of TGF beta 1 and leptin ameliorates thioacetamide-induced liver injury in lipopolysaccharide-primed rats

作者：Chen Huan Nan; Fan Sabrina; Weng Ching Feng^*

来源：Journal of Endotoxin Research, 2007, 13(3): 176-188.

DOI：10.1177/0968051907081102

• thioacetamide
• lipopolysaccharide
• endotoxin tolerance
• TGF beta 1
• leptin
• liver injury

Pretreatment with a low dose of bacterial endotoxin (lipopolysaccharide, LPS) caused the reduction of cytochrome P450 (CYP) enzymes and inflammatory factors which are capable of protecting the liver from a lethal LPS challenge. However, the effects of LPS pretreatment on the expression of transforming growth factor beta 1 (TGF beta 1) and leptin in thioacetamide (TAA)-induced liver fibrosis remain unknown. In this study, Sprague-Dawley rats were pretreated intraperitoneally with LPS (5 mg/kg body weight) for 24 h, and subsequently treated with TAA (200 mg/kg body weight/3 days) for I month to examine the effects of LPS on TAA-injured rats. LPS pretreatment was associated with lower granulation and lower (P < 0.05) GOT/GPT than in TAA-injured rats. The LPS-pretreated group had less collagen (Sirius red histochemical staining). Semiquantitative RT-PCR showed that the levels of collagen 3 and TGF beta 1 mRNAs were lower (P < 0.05) in the liver of LPS-pretreated rats than in TAA-injured rats. TGF beta RI mRNA in the liver of LPS-pretreated rats exceeded (P < 0.05) that in TAA-injured rats. LPS pretreatment reduced the leptin content (Western blot) below that of TAA-injured rats. These results imply that LPS pretreatment (endotoxin tolerance) alleviates the TAA-induced liver fibrosis of rats by reducing TGF beta 1 and leptin content.

• 出版日期2007
• 单位东华大学