OBJECTIVE To explore the mechanism of Ruangan Granule against CCl4-induced hepatic fibrosis in rats based on RhoA/ROCK pathway.METHODS The rat hepatic fibrosis model was established by intragastric administration of 40％CCl4(2 mL·kg-1)(CCl4∶olive oil=2∶3),twice a week for 8 weeks.After the intervention of Ruangan Granule at 6 week for 8 weeks,Masson staining,organ index and biochemical indexes were used to evaluate the effect of Ruangan Granule on CCl4-induced hepatic fibrosis in rats.RT-PCR,Westem blotting and immunofluorescent tissue chemistry was used to detected the expression of Coll Ⅰ,α-SMA,RhoA,ROCK 1 mRNA and protein in rats.RESULTS The organ index and biochemical analysis indicated that,compared with the model group,the liver index of rats was decreased in the middle dose group(P＜0.01),and the spleen index was decreased in the high and middle dose groups(P＜0.05 or P＜0.01);high,middle and low dose of Ruangan Granule could increase the thymus index of rats(P＜0.05 or P＜0.01);Ruangan Granule could reduce the levels of AFP,ALT and AST in the serum(P＜0.05 or P＜0.01).The results of Masson staining showed that Ruangan Granule could significantly reduce the proliferation of collagen fibers in rat liver.RT-PCR,immune fluorescent tissue chemistry results showed that Ruangan Granule could significantly downregulate the expression of Coll Ⅰ,α-SMA,RhoA,and ROCK 1 mRNA and protein.Westem blotting results showed the protein expression of Colli,α-SMA and Rock-1 were decreased in all groups.The protein expression of RhoA was decreased in middle and low dose groups of Ruangan Granule.CONCLUSION The therapeutic effect of Ruangan Granule on CCl4-induced hepatic fibrosis in rats may be related to the inhibition of RhoA/ROCK pathway.
维普
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