Balancing Effect of Biejiajian Oral Liquid(鳖甲煎口服液)on ACE-AngⅡ-AT1R Axis and ACE2-Ang-(1–7)-Mas Axis in Rats with CCl_4-Induced Hepatic Fibrosis

Objective： To explore the effect of Biejiajian Oral Liquid（鳖甲煎口服液, BOL） on CCl4-induced hepatic fibrosis in rats by detecting the changes in the levels of angiotensinⅡ（AngⅡ）, angiotensin-（1–7） [Ang-（1–7）], angiotensin-converting enzyme（ACE）, ACE2, angiotensinⅡ type 1 receptor（AT1 R）, Mas, etc. Methods： A total of 180 Wistar rats were randomly divided into two groups by random digital table method： prevention experiment and treatment experiment. Each group was further subdivided into the fol owing 6 subgroups： normal control group, model group, vitamin E [100 mg/（kg·d）, VE] group, enalapril [10 mg/（kg·g）, Ena] group, high-dosage [20 g/（kg·d）] BOL group, and low-dosage [10 g/（kg·d）] BOL group. The hepatic fibrosis rat model was established by subcutaneous injection of CCl4 for 6 weeks. Prevention experiment and treatment experiment were administered with specific drugs at different times. At the end of treatment experiment, the pathological changes of liver were observed after hematoxylin-eosin staining. The expressions of ingredients in renin-angiotensin-aldosterone system（RAAS） such as AngⅡ, Ang-（1–7）, ACE, ACE2, AT1 R, Mas, renin, CYP11 B2 and angen in liver were detected by enzyme linked immunosorbent assay, immunohistochemistry method or reverse transcription-polymerase chain reaction, respectively. Results： The levels of AngⅡ and Ang-（1–7） at the 6 th week increased by 496.10% and 73.64%, respectively, compared with those at the 2 nd week in the model group（P〈0.01）. With prevention or treatment with high-dosage BOL, there was an evident reduction of AngⅡ level but an improvement of Ang-（1–7） level. Specifically, AngⅡ level of high-dosage group decreased by 77.50% in prevention experiment（P=0.000） and by 76.93% in treatment experiment（P=0.002） compared with that in the model group. Ang-（1–7） level increased by 91.69% in prevention experiment（P=0.006） and by 70.77% in the treatment experiment（P=0.010） compared with that in the model group. The expression levels of m RNA of renin, ACE, CYP11 B2, angen and AT1 R decreased by 58.15%, 99.90%, 99.84%, 99.99% and 99.99%（al P〈0.01）, respectively. Conclusions： BOL could help resist liver fibrosis in rats by enhancing the level of each ingredient in ACE2-Ang-（1–7）-Mas axis, while decreasing the level of each ingredient in ACE-AngⅡ-AT1 R axis. To some extent, BOL could enhance the regulation of RAAS in rats with CCl4-induced hepatic fibrosis.