Objective:To investigate the expression of tissue inhibitor of metalloproteinases-1（TIMP-1）and type Ⅰ

Ⅲ collagen in carbon tetrachloride（CCl4）- induced liver fibrosis rats treated with small interference RNA（siRNA）targeting TIMP-1. Methods:A total of 32 male SD（Sprague Dawley）rats were randomly and averagely divided into 4 groups:normal group

model group

TIMP-1siRNA treatment group（0.25 mg/kg）

TIMP-1 siRNA negative control group（0.25 mg/kg）. CCl4 was used for 12 weeks to induce liver fibrosis. All rats were then sacrificed to collect liver tissue samples. A portion of the liver samples was soaked in formalin for testing the degree of liver fibrosis by hematoxylin-eosin staining. The expression of TIMP-1 and type Ⅰ

Ⅲ collagen was detected by immuno histochemical staining. TIMP-1 protein expression was detected by Western blot and TIMP-1 mRNA expression and type Ⅰ

Ⅲ collagen was measured by quantitative real-time polymerase chain reaction. Results:Compared with those in model group and negative control group

the tissue of liver in TIMP-1 siRNA treatment group has normal structure

with a small number of inflammatory cell infiltrating

and there is no obvious proliferation of collagen fibers. Immunohistochemistry showed the protein expressions of TIMP-1 and type Ⅰ

Ⅲcollagen were decreased significantly. Western blot showed the protein expression of TIMP-1 was decreased significantly. Real-time PCR showed that the mRNA expression of TIMP-1

type Ⅰcollagen and type Ⅲ collagen were decreased significantly. Conclusion:TIMP-1 siRNA can inhibit the expression of TIMP-1

and can effectively prevent the occurrence and development of liver fibrosis induced by CCl

4

in rats. The mechanism is the down-regulation of TIMP-1 expression can promote extracellular matrix degradation.