Therapeutic effects of Fuzhenghuayu decoction on nonalcoholic steatohepatic fibrosis rats by regulating ACE-Ang Ⅱ-AT1R axis / 解放军医学杂志

ABSTRACT

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 groupsnormal 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＜0.05),and the high-dose group showed the most robust decrease.Conclusions The Fuzhenghuayu decoction reduces nonalcoholic fatty hepatic fibrosis effectively,thereby leading to down-regulated the expressions of ACE-Ang Ⅱ-AT1R axis.These effects may represent the mechanism by which this drug suppresses hepatic fibrosis.