Effect of Chinese medicine Qinggan Huoxuefang on inducing HSC apoptosis in alcoholic liver fibrosis rats.
OBJECTIVE
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 (CCl(4))(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 CCl(4) in olive oil twice a week for 12 wk. The CCl(4) 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 (gamma-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 CCl(4) 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(1,972+/-366 vs 2,777+/-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.


CONCLUSIONS
QGHXF can improve liver fibrosis and induce HSC apoptosis.
Ji
Guang
G
Laboratory of Liver Disease, Long Hua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. jiliver@vip.sina.com
Wang
Lei
L
Zhang
Shui-Hua
SH
Liu
Jian-Wen
JW
Zheng
Pei-Yong
PY
Liu
Tao
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008104:Liver Cirrhosis, Alcoholic / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017208:Rats, Wistar
D004365:Drugs, Chinese Herbal