Objective: To investigate the mechanism of salvianolic acid B (Sal B) action against liver fibrosis through preventing lipid peroxidation and regulating MMP-2 activity in liver.
Method: The liver fibrotic model was induced through intraperitoneally injection of DMN at a dose of 10 microg x kg(-1) for every other day and lasting for 4 weeks. Sal B was administered (10 mg x kg(-1)), and perindopril (5 mg x kg(-1)) was used as positive control. Hepatic inflammation and collagen were observed with HE and sirius red staining. The liver function including serum ALT, AST activity, Alb and total bilirubin (T. Bil) level were determined. The hepatic lipid peroxidation including SOD and GST activities and GSH content were measured. Hepatic hydroxyproline (Hyp) content was detected with Jamall's method. The activity of metalloproteinase was assayed by gelatin zymography. The expressions of alpha-SMA, Col I in liver tissue were analyzed by Western blot.
Result: The model rats had higher serum T. Bil content, ALT and AST activities but lower Alb content than the normal rats, also had remarkable inflammatory necrosis and collagen deposition in liver, with much higher Hyp content, protein expression of alpha-SMA and collagen I and MMP-2 activity in liver, but had a decreased GSH content, SOD and GST activities. Both Sal B and perindopril attenuated hepatic injury and collagen deposition in model rats, decreased serum ALT activity and hepatic Hyp content, down-regulated alpha-SMA and collagen I protein expressions and metalloproteinase-2 activity than those in the model group, but increased SOD activity and GSH content, and Sal B decreased serum T. Bil content and increased GST activity. Sal B had a much better comprehensive actions than perindopril.
Conclusion: Sal B has a good preventive action against liver fibrosis, the action mechanism is related to the prevention from lipid peroxidation and down-regulation of metalloproteinase-2 activity in fibrotic liver.