[Effect of Panax notoginseng saponins on expressions of MMP-13 and TIMP-1 in rats with hepatic fibrosis].
OBJECTIVE
To investigate the effect of Panax notoginseng saponins (PNS) on the expressions of matrix metalloproteinase (MMP)-13 and its tissue inhibitor of metalloproteinase (TIMP)-1 in carbon tetrachloride (CCl4)-induced hepatic fibrosis rats, and explore the possible mechanism of PNS's effect against hepatic fibrosis.


METHODS
The rats were randomly divided into 6 groups: the normal group, the model group, PNS (50, 100, 200 mg x kg(-1)) treatment groups and the Col (0.1 mg x kg(-1)) group. Apart from the normal group, all of the remaining groups were subcutaneously injected with CCl4 twice a week for 18 weeks, in order to establish the hepatic fibrosis rat model. Since the 9th weeks, each treatment group was orally administered with corresponding drugs, and the normal group and the model group were orally administered with equal volume of normal saline for 10 weeks. After the end of the experiment, liver and spleen indexes were calculated; the levels of serum ALT and AST were measured by chromatometry. Liver tissues were collected to detect the pathological alteration HE staining; protein expressions of MMP-13 and TIMP-1 were determined with immuninochemistry. Moreover, MMP-13 and TIMP-1 mRNA expressions was detected by RT-PCR technology.


RESULTS
Compared with the model group, PNS (100, 200 mg x kg(-1)) significantly mitigated hepatic fibrosis in rats, reduced liver and spleen indexes, ALT and AST contents in serum, and TIMP-1 expression, and notably increased MMP-13 expression in rats with hepatic fibrosis.


CONCLUSIONS
P. notoginseng saponins have certain protective effect in rats with hepatic fibrosis. Its mechanism is related to up-regulating MMP-3, inhibiting TIMP-1 expression and improving collagen degradation.
The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Grade Three Laboratory of Traditional Chinese Medicine Preparations under State Administration of Traditional Chinese Medicine, Hefei 230031, China.
Hui
H
Jiang
Lun-Zhu
LZ
Xia
Ying
Y
Li
Xiang
X
Li
Jian
J
Wu
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D005786:Gene Expression Regulation / Q000187:drug effects; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D053723:Panax notoginseng / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D012503:Saponins / Q000008:administration & dosage / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D012503:Saponins; D019715:Tissue Inhibitor of Metalloproteinase-1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053509:Matrix Metalloproteinase 13