Effect of All-trans Retinoic Acid on Liver Fibrosis Induced by Common Bile Duct Ligation in Rats
Effect of All-trans Retinoic Acid on Liver Fibrosis Induced by Common Bile Duct Ligation in Rats作者机构：Department of Gastroenterology Pu'ai Hospital Tongji Medical College Huazhong University of Science and Technology Department of Gastroenterology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology
出 版 物：《Journal of Huazhong University of Science and Technology(Medical Sciences)》 (华中科技大学学报（医学英德文版）)
年 卷 期：2008年第28卷第5期
页 面：553-557页
核心收录：
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
主 题：liver fibrosis all-trans retinoic acid COL Ⅰ MMP2 MMP13 TIMP-1 CTGF TGF-β1
摘 要：The aim of this study was to investigate the effect and possible mechanism of all-trans retinoic acid （ATRA） on liver fibrosis induced by common bile duct ligation （CBDL） in rats. Fifty-three female Wistar rats were randomly divided into 5 groups： sham operation group （group J, 5 animals） and groups A, B, C and D （12 animals in each group）. The rats in groups A, B, C and D were subjected to CBDL to induce liver fibrosis, while those in group J to sham operation. From the 3rd week the rats in groups B, C and D respectively received daily administration of ATRA via gas- tric tube at three different doses [0.1, 1.5 and 7.5 mg/kg body weight （BW）]. Animals were sacrificed at 6th week. Rats＇ liver tissues were observed for pathologic changes under a light microscope. The protein levels of type Ⅰ collagen （COLⅠ）, matrix metalloproteinase-2 （MMP2）, MMP13 and tissue inhibitors of metalloproteinase-1 （TIMP-1） in liver tissues were determined by immunohistochemical techniques. The expression levels of TGF-β1 and CTGF mRNA in liver tissues were detected by semi-quantitative reverse transcription-polymerase chain reaction （RT-PCR）. The results showed that loss of normal hepatic architecture and formation of obvious fibrosis were observed in group A, while ATRA treatment for 4 weeks notably alleviated the pathological changes of hepatocytes. The expres- sion of COL Ⅰ and TIMP-1 proteins in group A was increased, while decreased in ATRA-treated CBDL groups （P〈0.05）. ATRA （1.5 and 7.5 mg/kg BW） reduced the expression levels of COLⅠ protein more greatly than that of 0.1 mg/kg BW （P〈0.05）. ATRA treatment increased the protein levels of MMP2 and MMP13. The expression levels of TGF-β1 and CTGF mRNA in group A were increased. In comparison with group A, the mRNA levels of TGF-β1 and CTGF in ATRA-treated CBDL groups were significantly decreased （P〈0.05）. It was concluded that ATRA could inhibit CBDL-induced liver fibrosis in rats by suppressing the expression of TGF-β1 and CTGF so as to
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