【摘 要】
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Objective:To explore the effect of Biejiajian Oral liquid(鳖甲煎口服液, BOL) on CCI4-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,angioten
【机 构】
：
Institute of Pharmacology, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University,
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Objective:To explore the effect of Biejiajian Oral liquid(鳖甲煎口服液, BOL) on CCI4-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·cl)] BOL group.The hepatic fibrosis rat model was established by subcutaneous injection of CCI4 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 Ang Ⅱ,Ang-(1-7),ACE,ACE2,AT1 R,Mas,renin,CYP11B2 and angen in liver were detected by enzyme linked immunosorbent assay,immunohistochemistry method or reverse transcription-polymerase chain reaction,respectively.Results:The levels of Ang Ⅱ 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).Wirth prevention or treatment with high-dosage BOL,there was an evident reduction of Ang Ⅱ level but an improvement of Ang-(1-7) level.Specifically,Ang Ⅱ 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.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-Ang Ⅱ-AT1R axis.To some extent,BOL could enhance the regulation of RAAS in rats with CCI4-induced hepatic fibrosis.
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