| Objective: To study the effect of traditional Chinese medicine-Ganfu- kang on the expression of Janus kinase 2(JAK2) and signal transducer and activator of transcription 3(STAT3) in rat with experimental liver fibrosis, and explore its therapy mechanism of action on JAK2/STAT3 pathway.Methods: SD rats were randomly divided into normal control group(C), model group(M), model control group(MC), high dose treatment group(HT), middle dose treatment group(MT), low dose treatment group(LT) and me- dicine prevention group(P). The hepatic fibrosis in rats except normal con- trol group were injected by 10% CCl4 for 12 weeks. P group rats were trea- ted with Ganfukang and CCl4 simultaneously for 12 weeks. HT, MT and LT group were treated with Ganfukang from 9th week to 20th week. C group, M group and MC group were treated with the same capacity of sodium chloride. M and P group rats were killed at the end of 12th week and dislodge liver tissues quickly. The remaining rats were killed at the end of 20th week by the same way. The levels of serum alanine aminotransferase(ALT), aspar- tate aminotransferase(AST), albumin, total protein were measured. The pathological changes of hepatic tissues were observed under light mic- roscopy by HE staining. The tissue inhibitor of metalloproteinase -1 (TIMP -1) of hepatic tissues were measured by immunohistochemistry staining. Hepatic Janus kinase 2(JAK2)and signal transducer and activator of transcription 3(STAT3) were detected by reverse polymerase chain reaction (RT-PCR).Results: (1) Serum index: At the end of 20th week, compared with M group, the levels of serum ALT decreased(P<0.01), AST decreased(P<0.01), albumin increased(P<0.01), globulin decreased(P<0.01), the ratio of albu- min and globulin increased(P<0.01) in MT group. (2) The pathological changes of hepatic tissues: HE staining displayed the structure of hepatic lobules in M group disordered and fibrilla increased. The structure of hepatic lobules in the MT group improved obviously compared with those in M group. (3) Expression of TIMP-1: In the hepatic tissue of rats in C group, few TIMP-1 positive staining cells were observed by immunohistochemistry staining. The quantity of TIMP-1 positive staining cells of liver tissue in M group increased obviously comparison with those in C group. TIMP-1 positive staining cells in MT group were less than those in M group evi- dently (p<0.01). (4)Expression of JAK2 and STAT3 mRNA: RT-PCR analysis showed that liver tissue of C group had low but detectable levels of JAK2 and STAT3 mRNA. Rats in M group showed higher JAK2 and STAT3 levels in liver tissue. The levels decreased in MT group comparison with those in M group, the difference was significant (p<0.01).Conclusion: (1)JAK2/STAT3 signal transduction pathway played an important role in hepatic fibrosis. (2)Ganfukang had therapeutic effect on hepatic fibrosis. Its mechanism of action may be related to decrease the expression of JAK2 and STAT3 of hepatic tissue and block JAK2/STAT3 signal transduction pathway.
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