Alleviating effects of dehydrocavidine on carbon tetrachloride-induced hepatic fibrosis in rats
Objective To investigate the alleviating effects and their possible mechanism of dehydrocavidine on carbon tetrachloride(CCl4)-induced hepatic fibrosis in rats.Methods SD rats were randomized into normal group,model group,silibinin group(30 mg/kg),and dehydrocavidine group(50 mg/kg),with six rats in each group.Except for normal group,the other three groups were injected intraperitoneally with 30%CCl4 olive oil solution(1 mL/kg)to establish the hepatic fibrosis model,twice a week for 14 weeks.At the 13th and 14th weeks of modeling,each medication group was given the corresponding drug at the set dose intragastrically every day.Meanwhile,normal and model groups were given the equal volume of normal saline intragastrically.After 12 h of the last administration,the rat hepatic and splenic tissue were collected to measure the hepatic and splenic indexes;HE staining and Masson staining were used to observe the histopathological changes of the liver;colorimetric method was carried out to determine the content of alanine aminotransferase(ALT),aspartate aminotransferase(AST),malondialdehyde(MDA),and superoxide dismutase(SOD)in rat serum.ELISA was performed to measure the expression levels of serum hyaluronic acid(HA),laminin(LN),typeⅢprocollagen(PCⅢ)and collagenⅣ(ColⅣ);Western blot was applied to examining the protein expression levels of transforming growth factor β1(TGF-β1),α-smooth muscle actin(α-SMA),E-cadherin,and N-cadherin in the liver tissue.Results Compared with normal group,the hepatic and splenic indexes of rats in model group significantly increased(P＜0.001),the degree of hepatic fibrosis was remarkable,and the collagen volume fraction was significantly elevated(P＜0.001);meanwhile,the serum levels of ALT,AST,MDA,LN,HA,PCⅢ,and Col Ⅳ were fairly higher(P＜0.001),while the level of SOD was obviously lower(P＜0.001);the protein expression levels of TGF-β1,α-SMA,and N-cadherin in the liver tissue were significantly up-regulated(P＜0.001),while that of E-cadherin was obviously down-regulated(P＜0.001).Compared with model group,the hepatic and splenic indexes of rats in dehydrocavidine group were significantly reduced(P＜0.001),the histopathological damage and fibrous hyperplasia were effectively alleviated,and the collagen volume fraction decreased significantly(P＜0.001);the serum levels of ALT,AST,and MDA were significantly lower(P＜0.001),while that of SOD was significantly higher(P＜0.001);the serum expression levels of LN,HA,PCⅢ,and Col Ⅳ were obviously up-regulated(P＜0.05,P＜0.001);the protein expression levels of TGF-β1,α-SMA,and N-cadherin in the liver tissue markedly decreased(P＜0.001),while that of E-cadherin significantly increased(P＜0.001).Conclusion Dehydrocavidine can alleviate hepatic fibrosis in rats significantly,the mechanism of which may be related to the intervention in the oxidative stress,down-regulation of N-cadherin,α-SMA,and TGF-β1 protein expressions,and up-regulation of E-cadherin protein expression in the liver tissue.
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