Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 28, 2005; 11(4): 561-566
Published online Jan 28, 2005. doi: 10.3748/wjg.v11.i4.561
In vivo effects of Chinese herbal recipe, Danshaohuaxian, on apoptosis and proliferation of hepatic stellate cells in hepatic fibrotic rats
Xiao-Xia Geng, Qin Yang, Ru-Jia Xie, Xin-Hua Luo, Bing Han, Li Ma, Cheng-Xiu Li, Ming-Liang Cheng
Xiao-Xia Geng, Ming-Liang Cheng, Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, Guizhou Province, China
Qin Yang, Ru-Jia Xie, Bing Han, Department of Pathophisiology, Guiyang Medical College, Guiyang 550004, Guizhou Province, China
Xin-Hua Luo, Department of Infectious Diseases, People’s Hospital of Guizhou Province, Guiyang 550004, Guizhou Province, China
Li Ma, Central Laboratory, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, Guizhou Province, China
Cheng-Xiu Li, Department of Pharmacology, Guiyang Medical College, Guiyang 550004, Guizhou Province, China
Author contributions: All authors contributed equally to the work.
Correspondence to: Ming-Liang Cheng, Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, 28# Guiyi street, Guiyang 550004, Guizhou Province, China. chengml@21cn.com
Telephone: 13985033971 Fax: +86-851-6741623
Received: March 15, 2004
Revised: March 17, 2004
Accepted: April 16, 2004
Published online: January 28, 2005
Abstract

AIM: To investigate the effects of Danshaohuaxian (DSHX), a Chinese herbal recipe, on the apoptosis and cell cycles of hepatic stellate cells (HSCs) in rat hepatic fibrosis and its possible mechanisms.

METHODS: Seventy-six male Wistar rats were randomly divided into normal control group, hepatic fibrosis group, non-DSHX-treated group and DSHX-treated group. Except for the normal control group, rat hepatic fibrotic models were induced by subcutaneous injection of carbon tetrachloride (CCl4), drinking alcohol, giving diet of hyperlipid and hypoprotein for 8 wk. When the hepatic fibrotic models were produced, 12 rats of hepatic fibrosis group (15 rats survived, others died during the 8 wk) were sacrificed to collect blood and livers. HSCs were isolated from the other 3 rats to detect the apoptotic index (AI) and cell cycles by flow cytometry. DSHX was then given to the DSHX-treated group (1.0 g/kg, PO, daily) for 8 wk. At the same time, normal control group and non-DSHX-treated group were given normal saline for 8 wk. At end of the experiment, some rats in these three groups were sacrificed to collect blood and livers, the other rats were used for HSC isolation to detect the apoptotic index (AI) and cell cycles. Then the liver index, serum hyaluronic acid (HA) and alanine aminotransferase (ALT), degree of hepatic fibrosis, urinary excretion of hydroxyproline (Hyp) and expression of collagen types I and III (COL I and III) in these four groups were detected respectively.

RESULTS: Compared with the indexes of the hepatic fibrosis group and non-DSHX-treated group, the DSHX-treated group revealed a liver index of (0.0267±0.0017 vs 0.0423±0.0044, 0.0295±0.0019, P<0.05), levels of serum HA (200.78±31.71 vs 316.17±78.48, 300.86±72.73, P<0.05) and ALT(93.13±5.79 vs 174.5±6.02, 104.75±6.54, P<0.01), and stage of hepatic fibrosis (1.30 vs 4.25, 2.60, P<0.01) all reduced. The urinary excretion of Hyp increased (541.09±73.39 vs 62.00±6.40, 182.44±30.83, P<0.01), the COL I and III expression decreased (COL I: 1.07±0.96 vs 4.18±2.26, 3.22±1.44, P<0.01; COL III: 1.09±0.58 vs 3.04±0.62, 2.23±0.58, P<0.01), the HSCs apoptotic index of HSCs (7.81±0.47 vs 1.63±0.25, 1.78±0.4, P<0.05) and the ratio of G0-G1 phase cells increased (94.30±1.33 vs 62.27±17.96, 50.53±2.25, P<0.05). The ratios of S-phase cells (3.11±1.27 vs 9.83±1.81, 11.87±1.9, P<0.05) and G2-M phase cells (2.58±0.73 vs 23.26±10.95, 13.60±1.15, P<0.01) declined.

CONCLUSION: DSHX capsule shows certain therapeutic effects on hepatic fibrosis in rats and inhibits abnormal deposition of COL I and III in rat livers by promoting the apoptosis of HSCs and preventing their proliferation.

Keywords: Hepatic fibrosis, Hepatic stellate cells, Danshaohuaxian, Apoptosis, Cell proliferation