Dynamic Evolution Of Angiotensin-converting Enzyme (ACE)2 And Angiotensin-(1-7) During Liver Fibrosis

Objective:To obtain the dynamic evolution of Angiotensin-converting Enzyme (ACE)2 and Angiotensin-(1-7) during experimental liver fibrosis through the establishment of CCL4-induced liver fibrosis in rats. To explore the protective effects of Angiotensin-converting Enzyme 2 and Angiotensin-(1-7) in liver fibrosis, so as to seek and enrich effective methods for clinical treatment of liver fibrosis.Methods:36 wister rats were randomly allocated into a normal group( n=6) and a model group (n=30).To induce live fibrosis,in a model group rats were given intraperitoneal injections of 40% phenixin two times per week, totally for 8 weeks.Firstly the dosage is 5ml/kg and secodly it is 2ml/kg. The dosage of drugs was adjusted according to body weight once a week. The control group gives the same dosage of oil intraperitoneal injection. 6 rats in the model group were killed at 2,4,6 and 8 weeks. Histopathological study of liver tissue was done with hematoxylin-eosin (HE) and Masson trichrome staining.All rats were examined portal vein pressure and ALT.Ang-(1-7) was determined by Enzyme-linked immunosorbent assay (ELASA). ACE2 was assessed by immunohistochemical staining.Results:(1)Morphological studies showed that there was an increasing degree of hepatic fibrosis in rats of the model group compared with that of the control group.(2)The level of serum ALT showed a gradual upward trend change and they are higher than normal control group(P<0.05 or P<0.01 ).(3)The mean±SD of portal vein pressure at 2 and 4 weeks are 8.43±0.86 and 12.26±1.31.They are higher than normal control group(4.65±0.55)(P<0.05). Week 6 and Week 8 were more higher( 15.03±2.29 and 16.22±2.08)and significantly higher than the normal group(4.65±0.55)(P<0.01).(4)The level of plasma Ang-(1-7) at 4 weeks is higher than normal control group(P<0.05).Week 6 and Week 8 were more higher and significantly higher than the normal group(P<0.01)(5)Immunoreactivity showed that few cells expressed ACE2 protein in livers from control rats. At 2 weeks and 4 weeks, only a small part of the liver cells expressed ACE2. Hepatic ACE2 expression was markedly increased at 6 weeks and 8 weeks.Conclusion: ALT and portal vein pressure increase during liver fibrosis and ACE2 and Ang-(1-7) increase also. ACE2 and Ang-(1-7) relate with liver fibrosis.