Ferulic Acid Reduces The Liver Fibrosis Rat Portal Vein Pressure Through The RhoA Signaling Pathway-A Preliminary Research

Objective Liver cirrhosis is a common disease and one of the leading causes ofdeath in China, which is characterized by the diffuse fibrosis in liver tissue, theformation of false lobules and regenerative nodules. Portal hypertension and thedamage to liver function are the main performances. In order to look for new thera-peutic targets, deep exploration of its pathogenesis is necessary. Some previousstu dy s have con firme d that t he activatio n of Rh o A sig naling path wayinvolved in the formation of liver fibrosis and portal hypertension, and inducedmorphological changes of the HSC. Ferulic acidcan effectively reduce portal veinpressure and improve liver fibrosis of cirrhotic patients. But the exact mechanismhas not been elucidated. This experiment will try to reveal the molecular mechanismby which ferulic acid directly alleviates the portal hypertension of liver fibrosisrats, and provide a scientific basis and new ideas for clinical treatment of portalhypertension.Methods Rat model of cholestatic liver cirrhosis was made by bile duct ligation(BDL). Then rats were randomly divided into sham operation group (n=24), BDLgroup (n=28) and ferulic acid treatment group (n=21). The effect of ferulic acid onportal pressure in liver fibrosis rats was evaluated by in situ liver perfusion. On this basis, The HE staining was used to confirm the success of liver fibrosis model, andwe detected the expression of-SMA in fibrosis liver tissue by usingimmunohistochemical methods, Western blot and immunohistochemistry were used todetect the expressional levels of related molecules of RhoA signaling pathway inexperimental rat liver tissues. In addition, HSC were isolated from the normal rat livertissues by means of the modified Friedman method, and then identifed by thedouble-labeled fluorescence immunohistochemistry.Results This experiment successfully separated the HSC from normal rats, andIdentified them by double labeled immunofluorescence method. The results of insitu hepatic perfusion method suggested that ferulic acid could reduce the the portalvein pressure of the BDL liver fibrosis rats model in the overall level(*p﹤0.05versus sham;#p﹤0.05versus BDL); The HE staining confirmed the success of liverfibrosis model; by using immunohistochemical methods, we found that the number ofthe positive expression of-SMA cells increased in fibrosis liver tissue. Western blotmethod was used to detect the expression of RhoA signaling pathway moleculesin the three groups of rat liver and found that: comparing with the sham operationgroup, RhoA expression in the liver tissue of the BDL group increased(*P<0.05),eNOS, p-eNOs and p-VASP expression decreased(*P<0.05); comparing with the liverBDL group, RhoA expression increased after ferulic acid treatment(**P<0.05),eNOS, p-eNOs and p-VASP expression representing an increasing trend(**P<0.05).Conclusion Ferulic acidcan can effectively reduce portal vein pressure of BDLcirrhotic rat through the intervention of RhoA signal pathway.