RESUMO
<p><b>OBJECTIVE</b>To explore the effect of Biejiajian Oral Liquid (, BOL) on CCl-induced hepatic fibrosis in rats by detecting the changes in the levels of angiotensin II (Ang II), angiotensin-(1-7) [Ang-(1-7)], angiotensin-converting enzyme (ACE), ACE2, angiotensin II type 1 receptor (AT1R), 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 following 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 CCl 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, AT1R, Mas, renin, CYP11B2 and angen in liver were detected by enzyme linked immunosorbent assay, immunohistochemistry method or reverse transcription-polymerase chain reaction, respectively.</p><p><b>RESULTS</b>The levels of AngII and Ang-(1-7) at the 6th week increased by 496.10% and 73.64%, respectively, compared with those at the 2nd 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 mRNA of renin, ACE, CYP11B2, angen and AT1R decreased by 58.15%, 99.90%, 99.84%, 99.99% and 99.99% (all P<0.01), respectively.</p><p><b>CONCLUSIONS</b>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-AT1R axis. To some extent, BOL could enhance the regulation of RAAS in rats with CCl-induced hepatic fibrosis.</p>
RESUMO
Objective] To explore the effect of Biejiajian oral Liquid (BOL) on the level of angiotensinⅡ(AngⅡ) and angiotensin(1-7) [Ang(1-7)],and ratio of AngⅡ/Ang(1-7) in liver fibrosis rats. [Methods] Randomly divide male Wistar rats into blank group, model group, BOL groups of high dose and low dose, 10 in each. The model rats were injected with inactivated pig serum abdominally, 0.5mL for each, 2 times/w, for successive 8w. Other rats were injected with the same dosage and period of normal saline. After modeling, administer BOL 10g·kg-1 to low-dose groups rats, and 20g·kg-1 to high-dose group rats; give equal distilled water to blank and model groups, for successive 5 weeks of intragastric administration. The liver histopathology was examined by hematoxylin-eosin(HE) and Masson trichrome staining. Liver and spleen index were calculated. Levels of alanine transaminase(ALT) and aspartate aminotransferase(AST) in serum were assayed by automatic biochemistry detection instrument. Contents of hyaluronic acid(HA), laminin(LN), typeⅢprocollagen(PcⅢ) and type IV collagen(Ⅳ.C) in serum were detected by radioimmunoassay. AngⅡand Ang(1-7) levels were determined by enzyme linked immunosorbent assay. [Results] Compared with model group, the histological injury of liver in rats of BOL groups was relieved; serum levels of AST, ALT, HA, LN, PCⅢ and Ⅳ.C, and the content of AngⅡ in liver homogenate were decreased significantly than that of the model group. Ang(1-7) level was further increased, AngⅡ/Ang(1-7) ratio was decreased obviously in BOL groups. [Conclusion] BOL showed the protective function for hepatic fibrosis, the mechanisms of which may be associated with improvement of Ang(1-7) level, decrease of AngⅡlevel and the ratio of AngⅡand Ang(1-7).