Effects Of Benezepril On Ang-(1-7) And MRNA Of ACE2 And Mas Receptor In Rats With Hepatic Fibrosis

Objective:To observe the curative effect of angiotensin converting enzyme inhibitor benazepril in the treatment of liver fibrosis, to study the effect of benazepril on the expression of Ang-(1-7) and concentration of mRNA of ACE2 and Mas receptor in liver tissue of rats with hepatic fibrosis.To explore the mechanism of anti hepatic fibrosis of benazepril.Methods:40 clean male SD rats were randomly divided into 3 groups, 12 in control group, 14 in model group and 14 in benazepril group. In addition to the control group, other two groups of rats were subcutaneously injected with 40%CCL4 oil, 2 times a week, for the first time, the amount of 5ml/kg, followed by 2.0ml/kg, the control group always being subcutaneously injected with the same dose of oil. From the first day of model making,benazepril group were given 10mg/kg of benazepril irrigation, the other 2groups were given the same dose of normal saline every day to the end of the experiment.On the end of 6weeks and 8weeks of the expriment, 6 rats were killed of each group,and liver tissue were stained with HE and Masson. The concentration of Ang?and Ang-(1-7)was determined by enzyme linked immunosorbent assay,then calculate the ratio of Ang II/Ang-(1-7).The content of mRNA of ACE2 and Mas receptor in liver tissue was detected by real-time fluorescence quantitative PCR.Results:(1) pathological changes: compared with the control group, the degree of liver fibrosis of model group in rats were higher at 6 weeks and 8 weeks(P<0.01),the rats of benazepril group were less than the model group in liver fibrosis(P<0.05).(2) ELISA results:(1)the concentration of Ang?of liver tissue of the model group were higher than the normal control group(P<0.01), and the benazepril group were less than the model group(P<0.05),(2)the concentration of Ang-(1-7) of liver tissue of the model group were higher than the normal control group(P<0.01), and the benazepril group were higher than the model group(P<0.05),(3) the ratio of Ang II /Ang-(1-7): the model group were higher than the normal control group(P<0.01), and the benazepril group were less than the model group(P<0.05).(3) Real-time fluorescence quantitative PCR results : the content of mRNA of ACE2 and Mas receptor of the model group were higher than the normal control group(P < 0.01), compared with the model group, the content of mRNA of the benazepril group further increased(P < 0.05).Conclusion:(1) Benazepril could significantly attenuate the degree of hepatic fibrosis in CCL4-induced rats.(2)Benazepril may by inhibiting the generation of AngII,and increasing the concentration of Ang-(1-7), and show a decrease in the ratio of Ang?/(Ang)-(1-7),thus play the role of anti hepatic fibrosis.(3)From the molecular biology level, it is confirmed that Benazepril may increase the expression of ACE2 and Mas receptor,thus delaying the progression of liver fibrosis.