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Balancing Effect of Biejiajian Oral Liquid (鳖甲煎口服液) on ACE-Ang II-AT1R Axis and ACE2-Ang-(1–7)-Mas Axis in Rats with CCl4-Induced Hepatic Fibrosis

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Abstract

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 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 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, AT1R, 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 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.

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-AT1R axis. To some extent, BOL could enhance the regulation of RAAS in rats with CCl4-induced hepatic fibrosis.

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Authors and Affiliations

  1. Institute of Pharmacology, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 311400, China

    Xiao-ya Li, Xia-wei Bu & Li Yao

  2. Hangzhou Institute for Food and Drug Control, Hangzhou, 310014, China

    Yan Peng

  3. Department of Chemistry, Zhejiang University, Hangzhou, 310027, China

    Jia Yao

Authors
  1. Xiao-ya Li
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  2. Yan Peng
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  3. Xia-wei Bu
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  4. Jia Yao
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  5. Li Yao
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Corresponding author

Correspondence to Li Yao.

Additional information

Supported by the National Natural Science Foundation of China (No. 81173640); the Natural Science Foundation of Zhejiang Province, China (No. Y205335; LY16H280009) and the Science Foundation of Zhejiang Chinese Medical University (No. 2016ZG11)

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Li, Xy., Peng, Y., Bu, Xw. et al. Balancing Effect of Biejiajian Oral Liquid (鳖甲煎口服液) on ACE-Ang II-AT1R Axis and ACE2-Ang-(1–7)-Mas Axis in Rats with CCl4-Induced Hepatic Fibrosis. Chin. J. Integr. Med. 24, 853–859 (2018). https://doi.org/10.1007/s11655-017-2909-7

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