Effects of Danggui Buxue Decoction () on lipid peroxidation and MMP-2/9 activities of fibrotic liver in rats.
OBJECTIVE
To explore the mechanism of Danggui Buxue Decoction (, DBD) on the liver fifibrosis related to hepatic lipid peroxidation and matrix metalloproteinases (MMP) -2/9 activities.


METHODS
The liver fifibrosis in 28 rats was induced by an injection of carbon tetrachloride (CCl(4)) and fed with high lipid and low protein diet for 6 weeks, the model rats were randomly divided into the model group and DBD treated group, 14 in each group, and another 10 rats as the normal group were observed as well. Rats in the DBD group were administered with DBD at the dose of 6 g/kg body weight for 6 weeks since CCl(4) intoxication. The hepatic inflammation and fibrosis were examined with HE and Sirius red stain. The liver function including serum alanine aminotransamine (ALT), aspartate transamine (AST), albumin (Alb) and total bilirubin (TBIL), liver triglyceride (TG) and malondialdehyde (MDA) contents, superoxide dismutase (SOD) activity were assayed. Hepatic hydroxyproline (Hyp) content was detected with Jamall's method. The alpha-SMA expression was analyzed by immunohistochemistry and the Western blot. Liver MMP-2 mRNA was analyzed with Real-time PCR, and MMP-2/9 activities were measured with gelatin zymography and in situ zymography.


RESULTS
Compared with the normal group, the levels of ALT, AST and TBIL, the content of Hyp, TG and MDA were remarkably increased, the Alb content and SOD activity were signifificantly decreased in the model group (P<0.05), and higher levels of MMP-2 mRNA and MMP-2/9 activities (P<0.01), the hepatic fatty degeneration and collagen accumulation and fifibrosis at liver were observed. Compared with the model control, DBD group showed slighter hepatic fatty degeneration and collagen deposition, and had lower levels of ALT, AST and TBIL activities, lower contents of MDA, TG and Hyp, but higher SOD level and Alb content (P<0.05), and DBD also down-regulated MMP-2 mRNA expression and decreased MMP-2/9 activities in the fifibrotic livers (P<0.01).


CONCLUSIONS
The action of DBD against liver fibrosis is related to prevent lipid peroxidation and inhibit MMP-2/9 activities in the fibrotic livers.
Chen
Yuan
Y
Shuguang Hospital, Liver Disease Institute, Shanghai University of Traditional Chinese Medicine, China.
Chen
Qian
Q
Lu
Jing
J
Li
Feng-hua
FH
Tao
Yan-yan
YY
Liu
Cheng-hai
CH
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D055166:Hepatic Stellate Cells / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D051381:Rats; D017208:Rats, Wistar
D004365:Drugs, Chinese Herbal; D061965:Matrix Metalloproteinase Inhibitors; C477279:danggui buxue decoction; D002251:Carbon Tetrachloride; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9