Therapeutic effects of Fuzhenghuayu decoction on nonalcoholic steatohepatic fibrosis rats by regulating ACE-Ang Ⅱ-AT1R axis

Objective To evaluate the influence of Fuzhenghuayu decoction on fibrotic liver tissue and angiotensin- converting enzyme- angiotensin Ⅱ- angiotensin Ⅱ 1 receptor (ACE-Ang Ⅱ-AT1R) axis using a nonalcoholic fatty liver fibrosis rat model system. Methods Forty male Sprague-Dawley (SD) rats were randomly divided into the following groups: normal control group, liver fibrosis model group, and liver fibrosis model Fuzhenghuayu drug intervention at low-dose [0.75g/(kg.d)] group and high-dose [1.5g/(kg.d)] group. Except the normal control group, the other three groups were fed high-fat diet for 24 weeks to induce nonalcoholic hepatic fibrosis model. The drug intervention was administered via oral-gastric irrigation once daily for 6 times per week over a 6-week period. The rats were sacrificed at the end of 6 weeks for serum and liver tissue collection. The levels of serum total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST) were measured by standard biochemical assays. The Ang Ⅱ contents of plasma and liver tissue were surveyed and evaluated by the radioimmunoassay method. Liver pathology was detected using HE staining and Masson trichrome staining. The mRNA and protein expressions of ACE, AT1R, α-smooth muscle actin (α-SMA) in the liver tissue were evaluated with real time-PCR, immunohistochemical staining, respectively. Results Compared with the model group, the levels of serum ALT and AST in the low-dose group and high-dose group decreased conspicuously, especially in the high-dose group, with a statistically significant difference (P<0.05); While the difference in the levels of serum TC and TG between the three groups was not statistically significant. Compared with the normal control group, Ang Ⅱ levels in plasma and liver tissue significantly increased in the other three groups; Further more, there was no significant difference in the plasma Ang Ⅱ level between the three groups (P>0.05); While the level of liver tissue Ang Ⅱ decreased significantly in the low-dose group and high-dose group than that in model group (P<0.05). Compared with the model group, the extent of pathological changes in hepatic tissues ameliorated after Fuzhenghuayu intervention according to HE and Masson staining, especially in the high-dose group. According to real time-PCR and immunohistochemical staining, the mRNA and protein expressions of ACE, α-SMA and AT1R decreased significantly in low-dose group and high-dose group than that in model group (P