Feng-Rui Yang1, Bu-Wu Fang, Jian-Shi Lou. 1. Department of Pharmacology, Tianjin Medical University, No. 22, Qixiangtai Road, Heping District, Tianjin 300070, China.
Abstract
AIM: To explore the anti-fibrotic effect of Haobie Yangyin Ruanjian decoction (HYRD) on CCl(4)-induced hepatic fibrosis in rats and its modulation on the transforming growth factor (TGF) beta-Smad signaling pathway. METHODS: Fifty-six healthy Wistar rats were randomly divided into five groups: normal control group (n = 6), CCl(4)-induced hepatic fibrosis group (n = 14) and three treatment groups (the treated rats received HYRD via oral administration at daily dosages of 8.2, 2.5 and 0.82 g/kg, respectively) of HYRD (n = 12, respectively). Experimental hepatic fibrosis was induced by subcutaneous injection of carbon tetrachloride solution (CCl(4) dissolved in peanut oil, 4:6, V/V) with 0.5 mL/100 g body weight for the first time, and then 0.3 mL/100 g body weight twice a week for 8 wk. In the former 2 wk, rats were raised by feedstuff I (80% corn meal, 20% lard, 0.5% cholesterol). After 2 wk, they were raised by feedstuff II (corn meal and 0.5% cholesterol). Except for the control group, 30% alcohol solution was given orally to each rat every other day from the beginning, 1 mL for each rat. Liver function parameters and hepatic hydroxyproline content were detected by chromatometry. Serum levels of hyaluronic acid (HA), type IV collagen (CIV), type III precollagen (PCIII) and laminin (LN) were assayed with radioimmunoassay. Deposition of collagen was observed with hematoxylin-eosin staining and collagen staining. Gene expression of TGFbeta1 and Smad3 were detected with real-time reverse transcriptase-polymerase chain reaction and Western blotting, respectively. RESULTS: The serum levels of alanine transaminase and aspartate transaminase were increased in the model group compared with the control group (P < 0.01), and they were decreased in the three treatment groups compared with the model group. The serum levels of total protein and albumin were decreased in the model group and increased in the three treatment groups. The hepatic hydroxyproline content and serum levels of PCIII, HA, LN and CIV were markedly increased in the model group compared with the control group, and decreased in the treatment groups. The gene expression of TGFbeta1 and Smad3 was enhanced in the model group compared with the control group, and HYRD could down regulate their expression. CONCLUSION: HYRD can inhibit hepatic fibrosis induced by CCl(4) in rats, which is probably associated with its down-regulation on fibrogenic signal transduction of TGFbeta-Smad pathway.
AIM: To explore the anti-fibrotic effect of Haobie Yangyin Ruanjian decoction (HYRD) on CCl(4)-induced hepatic fibrosis in rats and its modulation on the transforming growth factor (TGF) beta-Smad signaling pathway. METHODS: Fifty-six healthy Wistar rats were randomly divided into five groups: normal control group (n = 6), CCl(4)-induced hepatic fibrosis group (n = 14) and three treatment groups (the treated rats received HYRD via oral administration at daily dosages of 8.2, 2.5 and 0.82 g/kg, respectively) of HYRD (n = 12, respectively). Experimental hepatic fibrosis was induced by subcutaneous injection of carbon tetrachloride solution (CCl(4) dissolved in peanut oil, 4:6, V/V) with 0.5 mL/100 g body weight for the first time, and then 0.3 mL/100 g body weight twice a week for 8 wk. In the former 2 wk, rats were raised by feedstuff I (80% corn meal, 20% lard, 0.5% cholesterol). After 2 wk, they were raised by feedstuff II (corn meal and 0.5% cholesterol). Except for the control group, 30% alcohol solution was given orally to each rat every other day from the beginning, 1 mL for each rat. Liver function parameters and hepatic hydroxyproline content were detected by chromatometry. Serum levels of hyaluronic acid (HA), type IV collagen (CIV), type III precollagen (PCIII) and laminin (LN) were assayed with radioimmunoassay. Deposition of collagen was observed with hematoxylin-eosin staining and collagen staining. Gene expression of TGFbeta1 and Smad3 were detected with real-time reverse transcriptase-polymerase chain reaction and Western blotting, respectively. RESULTS: The serum levels of alanine transaminase and aspartate transaminase were increased in the model group compared with the control group (P < 0.01), and they were decreased in the three treatment groups compared with the model group. The serum levels of total protein and albumin were decreased in the model group and increased in the three treatment groups. The hepatic hydroxyproline content and serum levels of PCIII, HA, LN and CIV were markedly increased in the model group compared with the control group, and decreased in the treatment groups. The gene expression of TGFbeta1 and Smad3 was enhanced in the model group compared with the control group, and HYRD could down regulate their expression. CONCLUSION: HYRD can inhibit hepatic fibrosis induced by CCl(4) in rats, which is probably associated with its down-regulation on fibrogenic signal transduction of TGFbeta-Smad pathway.
Authors: Martin J J Ronis; Leah Hennings; Ben Stewart; Alexei G Basnakian; Eugene O Apostolov; Emanuele Albano; Thomas M Badger; Dennis R Petersen Journal: Am J Physiol Gastrointest Liver Physiol Date: 2010-11-04 Impact factor: 4.052