Effect of Chinese medicine Qinggan Huoxuefang on inducing HSC apoptosis in alcoholic liver fibrosis rats

被引:26
作者
Ji, Guang [1 ]
Wang, Lei
Zhang, Shui-Hua
Liu, Jian-Wen
Zheng, Pei-Yong
Liu, Tao
机构
[1] Shanghai Univ Tradit Chinese Med, Longhua Hosp, Lab Liver Dis, Shanghai 200032, Peoples R China
[2] Shanghai Univ Tradit Chinese Med, Longhua Hosp, Clin Evaluat Ctr, Shanghai 200032, Peoples R China
[3] E China Univ Sci & Technol, Dept Pharm, Shanghai 200237, Peoples R China
关键词
Qinggan Huoxuefang; alcoholic liver fibrosis; apoptosis; gene array;
D O I
10.3748/wjg.v12.i13.2047
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Aim: To investigate the effect of Qinggan Huoxuefang (QGHXF) on improvement of liver function and pathology in rats, and to analyze the mechanism. Methods: Wistar rats were divided into three groups at random: normal control group (12), micro-amount carbon tetrachloride group (CCl4)(12) and model group A (60). The model group A was ingested with the mixture (500 mL/L alcohol, 8 mL/kg per day; corn oil, 2 mL/kg per day; pyrazole, 24 mg/kg per day) once a day and intraperitoneal injections of 0.25 mL/kg of a 250 mL/L solution Of CCl4 in olive oil twice a week for 12 wk. The CCl4 group received intraperitoneal injections only. At the end of 8 wk the model group A (60) was divided into 5 subgroups: model group, Xiaochaihu Chongji (XCH) group, QGHXF high dose group, moderate dose group and low dose group, and were given the drugs respectively. At the end of 12 wk, all the rats were killed and blood samples collected, as well as liver tissue. Blood samples were used for evaluation of alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (y-GT). Liver specimens were obtained for routine HE, apoptosis gene array and flow cytometry analysis. Results: A liver fibrosis animal model was successfully established. Fibrosis was obviously reduced in QGHXF high dose group, and no fibrosis formed in CCl4 group. Compared with model group the QGHXF group and XCH group could obviously decrease the level of ALT, AST, ALP, and GGT (P<0.05). QGHXF high dose group was better than XCH group in ALT (615 +/- 190 vs 867 +/- 115), and AST(1972 +/- 366 vs 2777 +/- 608). Moreover, QGHXF could reduce liver inflammation, fibrosis-induced hepatic stellate cell (HSC) apoptosis and regulate apoptosis gene expression. The HSC apoptosis rates of QGHXF groups were 22.4 +/- 3.13, 13.79 +/- 2.26 and 10.07 +/- 1.14, higher than model group, 6.58 +/- 1.04 (P<0.05). Compared to model group, 39 genes were up-regulated, 11 solely expressed and 17 down-regulated in high dose group. Conclusion: QGHXF can improve liver fibrosis and induce HSC apoptosis. (C) 2006 The WJG Press. All rights reserved.
引用
收藏
页码:2047 / 2052
页数:6
相关论文
共 35 条
[2]
Liver fibrosis [J].
Bataller, R ;
Brenner, DA .
JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (02) :209-218
[3]
The role of angiogenesis in a murine tibial model of distraction osteogenesis [J].
Carvalho, RS ;
Einhorn, TA ;
Lehmann, W ;
Edgar, C ;
Al-Yamani, A ;
Apazidis, A ;
Pacicca, D ;
Clemens, TL ;
Gerstenfeld, LC .
BONE, 2004, 34 (05) :849-861
[4]
Liver asialoglycoprotein receptor levels correlate with severity of alcoholic liver damage in rats [J].
Casey, CA ;
McVicker, BL ;
Donohue, TM ;
McFarland, MA ;
Wiegert, RL ;
Nanji, AA .
JOURNAL OF APPLIED PHYSIOLOGY, 2004, 96 (01) :76-80
[5]
Fan Kai, 2005, Zhonghua Gan Zang Bing Za Zhi, V13, P229
[6]
Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury [J].
Friedman, SL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (04) :2247-2250
[7]
Gu Sai, 2005, Zhonghua Gan Zang Bing Za Zhi, V13, P479
[8]
Mechanisms of spontaneous resolution of rat liver fibrosis - Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors [J].
Iredale, JP ;
Benyon, RC ;
Pickering, J ;
McCullen, M ;
Northrop, M ;
Pawley, S ;
Hovell, C ;
Arthur, MJP .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (03) :538-549
[9]
Mutation in collagen-I that confers resistance to the action of collagenase results in failure of recovery from CCl4-induced liver fibrosis, persistence of activated hepatic stellate cells, and diminished hepatocyte regeneration [J].
Issa, R ;
Zhou, XY ;
Trim, N ;
Millward-Sadler, H ;
Krane, S ;
Benyon, C ;
Iredale, J .
FASEB JOURNAL, 2002, 16 (13) :47-+
[10]
Apoptosis of hepatic stellate cells: involvement in resolution of biliary fibrosis and regulation by soluble growth factors [J].
Issa, R ;
Williams, E ;
Trim, N ;
Kendall, T ;
Arthur, MJP ;
Reichen, J ;
Benyon, RC ;
Iredale, JP .
GUT, 2001, 48 (04) :548-557