[Effects of Shaoqiduogan on MMP-13, TIMP-1 expression in liver and hepatic stellate cells of hepatic fibrosis rats].
OBJECTIVE
To investigate the effects of Shaoqiduogan (SQDG) on the expression of matrix metalloproteinase 13 (MMP-13) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in carbon tetrachloride (CCl4) induced hepatic fibrosis rats and transforming growth factor beta1 (TGF-beta1) irritated hepatic stellate cells (HSC), and to explore its possible mechanisms.


METHODS
The model of chemical hepatic fibrosis induced by CCl4 was prepared. The rats were randomly divided into 5 groups, including normal control group, liver fibrosis model group and SQDG (42. 5, 85, 170 mg x kg(-1)) treated groups. The level of collagen type 1 (C-1) in serum was determined by radioimmunoassay. Masson stain was used to examine the histopathological change. MMP-13 and TIMP-1 ex-pression in liver tissues were assayed by immunohistochemistry. In vitro, effects of SQDG on the expression of MMP-13, TIMP-1 and C-1 in HSC-T6 stimulated by TGF-beta were measured by Western-blot.


RESULTS
The results showed that SQDG significantly decreased the elevated level of C-1 in serum of hepatic fibrosis rats induced by CCl4. Pathological examination showed that SQDG could remarkably alleviate the degree of liver fibrogenesis and formation of pseudolobulus. The results of immunohistochemistry demonstrated that SQDG significantly increased MMP-13 expression and decreased TIMP-1 expression in liver tissues. Furthermore, SQDG (20-160 mg x L(-1)) could facilitate MMP-13 expression, inhibit TIMP-1 expression and significantly inhibit the C-I production of HSC stimulated with TGF-beta1 in vitro.


CONCLUSIONS
The anti-fibrotic effects of SQDG may be associated with its action of promoting collagen degradation via controlling the levels of MMP-13 and TIMP-1 in liver.
Sun
Wuyi
W
Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immunopharmacology of Education Ministry, Anhui Engineering Technology Research Center of Anti-inflammatory and Immunodrugs, Hefei 230032, China.
Gui
Shuangying
S
Wu
Li
L
Wang
Hua
H
Wei
Wei
W
D000818:Animals; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D015870:Gene Expression / Q000187:drug effects*; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics* / Q000378:metabolism
D004365:Drugs, Chinese Herbal; D019715:Tissue Inhibitor of Metalloproteinase-1; D053509:Matrix Metalloproteinase 13