Effect Of Benazepril On NOX4 And Nrf2 In Rats With Hepatic Fibrosis

Objective:To explore the effects of benazepril,an angiotensin-converting enzyme inhibitor,on NOX4 and Nrf2 in rats with liver fibrosis.To explore the mechanism of anti-fibrosis of angiotensin-converting enzyme inhibitors.Methods:Twenty-two healthy male SD rats of clean grade were divided into 3 groups with random probability: control group(n=6),model group(n=8)and treatment group(n=8).The model treatment group was given 40% carbon tetrachloride subcutaneous injection,the initial dose was 5ml/kg,and then the dose was 2ml/kg,twice a week,for 8weeks;the control group was given the same dose of oil subcutaneous injection,twice a week,for 8 weeks.At the same time of model establishment,the treatment group was intragastrically administered with benazepril at a dose of 10 mg/(kg · d),and the control group and the model group were intragastrically administered with the same dose of normal saline for 8 weeks.All three groups of rats were given normal diet,and 6 rats in each group were randomly sacrificed on the 56 th day of the experiment,and the liver tissue at the same site was obtained for future use.Results:1.Macroscopic observation: The livers of rats in the control group were normal in volume,reddish-brown,soft,with smooth surface and edges,and good tissue elasticity.Compared with the control group,the livers of rats in the model group were reduced in size,harder in quality,and had plaguable granular changes on the surface.After bennazepril treatment,the granular changes on the surface of the liver in rats were reduced compared with the model group.2.Histopathology: In the control group,the liver structure was normal and the hepatic lobule structure was intact.Compared with the control group,the model group showed significant degeneration and necrosis,destruction of hepatic lobular structure,pseudolobule formation,and massive inflammatory cell infiltration.Compared with the model group,the degeneration and necrosis of liver tissue were alleviated and the fibrous cords were narrower in the treatment group than in the model group.3.Effects of bennazepril on NOX4 and Nrf2 expression in liver tissue:NOX4: Under light microscopy,it can be seen that NOX4-positive protein is brownish-yellow,mainly located in hepatocyte cytoplasm,fiber spacing and some vascular endothelial cells.Compared with the control group,the average optical density value of NOX4-positive protein in the liver tissue of the model group was increased and the difference was statistically significant(P<0.05).The average optical density value of NOX4-positive protein in the liver tissue of rats in the treatment group was significantly lower than that in the model group(P<0.05).Nrf2: Under light microscopy,the Nrf2-positive protein is brownish-yellow and localized to the cytoplasm of hepatocytes.Compared with the control group,the average optical density value of Nrf2-positive protein in the liver tissue of the model group was increased and the difference was statistically significant(P<0.05).The average optical density value of Nrf2-positive protein in the liver tissue of rats treated with bennazepril was significantly higher than that in the model group(P<0.05).Conclusion:Benazepril reduces liver fibrosis by reducing the production of angiotensin II.,inhibiting the activation of NOX4 and increasing the expression of Nrf2.