Action mechanism of Yi Guan Jian Decoction on CCl4 induced cirrhosis in rats.
OBJECTIVE
To investigate action mechanism of Yi Guan Jian Decoction on cirrhosis induced by CCl(4) in rats.


METHODS
CCl(4) (3 mL/kg) for the first time and then olive oil CCl(4) solution 50% (2 mL/kg) was administered hypodermically to rats twice each week for 12 weeks. At the end of 8th week, rats were randomly divided into CCl(4) control group (n=10), Yi Guan Jian Decoction group (n=9) and Xiao Chai Hu Decoction group (n=9). Yi Guan Jian Decoction and Xiao Chai Hu Decoction were oral administrated per day respectively for 4 weeks, concomitantly continued CCl(4) administration. At 12th weekend, the rats were sacrificed for sampling and detection of liver function, histological changes of liver tissue, liver tissue hydroxyproline content and expression of alpha-SMA, CD68, MMP-13, TIMP-1, TIMP-2, Caspase-12, HGFalpha, MMP-2, MMP-9 and hepatocyte apoptotic index.


CONCLUSIONS
(1) Compared with that of normal rats, expression of alpha-SMA, CD68 and TIMP-1 in liver tissue of 8 week model group rats increases significantly (P<0.01), moreover further increased in the 12 week of model group. However, MMP-13, HGFalpha, TIMP-2 content decreases gradually and the statistical difference is seen between each time point (P<0.01). Activity of MMP-2, MMP-9, content of Caspase-12 and hepatocyte apoptotic index increased gradually at 4th, 8th, 12th week. (2) Compared to that of the same time point model group, activity of MMP-9 and contents of MMP-13, TIMP-2 and HGFalpha in Yi Guan Jian Decoction group improves significantly (P<0.01), and activity of MMP-2 and contents of alpha-SMA, TIMP-1, Caspase-12 and hepatocyte apoptotic index decreases significantly (P<0.01). This work suggests that Yi Guan Jian Decoction exerts significant therapeutic effect on CCl(4)-induced cirrhosis in rats, through mechanism of inhibiting hepatocytes apoptosis and hepatic stellate cells activation, and regulating the function of Kupffer cell.


BACKGROUND
This study investigates the mechanism of Yi Guan Jian against cirrhosis from aspect of heptocytes apoptosis and hepatic stellate cells activation. It suggest that although of unknown bioactive ingredients, mechanism of traditional Chinese medicine recipe against cirrhosis can be disclosed and of profound significance.
Mu
Yongping
Y
Institute of Liver Diseases, Shuangguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Liu
Ping
P
Du
Guangli
G
Du
Jinxing
J
Wang
Gaoqiang
G
Long
Aihua
A
Wang
Lei
L
Li
Fenghua
F
D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002251:Carbon Tetrachloride; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use*; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000473:pathology; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D006909:Hydroxyproline / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008517:Phytotherapy; D051381:Rats; D017208:Rats, Wistar
D004365:Drugs, Chinese Herbal; C539461:Yi Guan Jian Decoction; D002251:Carbon Tetrachloride; D006909:Hydroxyproline