Effects of losartan intervention on regulation of collagen expression by angiotensin ¢ò type 1 receptor in liver fibrosis rat models

    WANG Weiª²Wei, YANG Xiª²Shan, LI Xu, WANG Jie, TIAN Ye, LAI Huangª²Wen, YANG Chuanª²Hong, LAI Riª²Quan

    1Department of Gastroenterology, General Hospital, Guangzhou Military Area Command, Guangzhou 510010, China, 2Institute for Digestive Diseases of PLA, First Military Medical University, Guangzhou 510515, China

    ¡¾Abstract¡¿ AIM: To investigate the expression of angiotensin ¢ò type 1 receptor (AT1R) and the effects of losartan intervention on the synthesis of collagen. METHODS: Thirtyª²six Wister rats were randomly divided into three groups: healthy control group (A), fibrosis model group ( B ) and fibrosis + losartan intervention group (C ). All rats, except the rats in control group, were given subcutaneous injection of 40% carbon tetrachloride (once every 3 days for 6 weeks). The rats in group C were also given losartan of 10 mg/kg daily for 6 weeks via gastrogarage, respectively. At the end of the sixth week, all rats were sacrificed . Van Giesion collagen staining was used to evaluate the extracellular matrix of the liver tissues and the ultrastructures of liver were observed by electron microscopy. The expression of AT1R was detected by indirect immunofluorescent microscopy and the protein or mRNA expression of collagen¢ñ, ¢ó in liver tissues was observed using immunohistochemistry or in situ hybridization methods. The relative contents of collagen¢ñ, ¢ó and procollagen¢ñ, ¢ó mRNA in liver tissues were calculated by image analyzer. RESULTS: ¢Ù Under light microscopy, the fibrotic degrees in group C were significantly lower than those in group B (P<0.05). ¢Ú The AT1R positive cells in group B significantly increased than those in group A (P<0.01), but in group C they decreased significantly than those in group B (P<0.01). ¢Û Collagen¢ñ, ¢ó and procollagen¢ñ, ¢ó mRNA expressions in liver tissues significantly increased in group B than those in group A(P<0.01, P<0.05), but in group C they decreased significantly than those in group B (P<0.01, P< 0.05). ¢Ü Significantly positive correlations were found between the AT1R and collagen¢ñ, ¢ó expressions (P<0.01, 0.01), and between the procollagen¢ñ, ¢ó mRNA expressions (P<0.01, 0.01). CONCLUSION: Losartan can reduce the collagen expression by inhibiting Ang¢òand its receptor AT1R. ......