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

Xiao-ya Li; Yan Peng; Xia-wei Bu; Jia Yao; Li Yao

doi:10.1007/s11655-017-2909-7

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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

OriginalPaper | Updated：2021-08-27

- 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
- 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
- 中国结合医学杂志（英文版） 2018年24卷第11期页码：853-859
- Affiliations：
  
  1. Institute of Pharmacology, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University,Hangzhou,China
  2. Hangzhou Institute for Food and Drug Control,Hangzhou,China
  3. Department of Chemistry, Zhejiang University,Hangzhou,China
- Author bio：
- Funds：
  
  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)
- DOI：10.1007/s11655-017-2909-7
  中图分类号：
- 纸质出版日期：2018，
  
  网络出版日期：2018-1-15，
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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

Xiao-ya Li, Yan Peng, Xia-wei Bu, 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[J]. Chinese Journal of Integrative Medicine, 2018,24(11):853-859.
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 DOI：

Xiao-ya Li, Yan Peng, Xia-wei Bu, 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[J]. Chinese Journal of Integrative Medicine, 2018,24(11):853-859. DOI： 10.1007/s11655-017-2909-7.

摘要

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. 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. 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. 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.

Abstract

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

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

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. 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

ACE

CYP11B2

angen and AT1R decreased by 58.15%

99.90%

99.84%

99.99% and 99.99% (all P<0.01)

respectively. 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.

关键词

Hepatic FibrosisBiejiajian Oral Liquidrenin-angiotensin-aldosterone systemcarbon tetrachlorideChinese Medicine

Keywords

Hepatic FibrosisBiejiajian Oral Liquidrenin-angiotensin-aldosterone systemcarbon tetrachlorideChinese Medicine

references

Andrea B, Cluadia M, Alice C, Alession G, Virginia C, Francesco M, et al. Extracellular matrix molecular remodeling in human liver fibrosis evolution. PLoS One 2016;11:e0151736.

Su TH, Kao JH, Liu CJ. Molecular mechanism and treatment of viral hepatitis-related liver fibrosis. Int J Mol Sci 2014;15:10578–10604.

Ning ZW, Luo XY, Wang GZ, Li Y, Pan MX, Yang RQ, et al. MicroRNA-21 mediates angiotensin II-induced liver fibrosis by activating NLRP3 inflammasome/IL-1β axis via targeting Smad7 and Spry1. Antioxid Redox Signal 2017;27:1–20.

Drapkina OM, Drapkina IuS. Heart and liver fibrosis: the components of a single equation. Kardiologiia 2014;54:57–62.

Moreira de Macêdo S, Guimarães TA, Feltenberger JD, Sousa Santos SH. The role of renin-angiotensin system modulation on treatment and prevention of liver diseases. Peptides 2014;62:189–196.

Kim G, Kim J, Lim YL, Kim MY, Baik SK. Renin-angiotensin system inhibitors and fibrosis in chronic liver disease: a systematic review. Hepatol Int 2016;10:819–828.

Wen B, Sun H, He S, Cheng Y, Jia W, Fan E, et al. Effects of Biejiajian Pills on Wnt signal pathway signal molecules β-catenin/TCF4 complex activities and downstream proteins cyclin D1 and MMP-2 in hepatocellular carcinoma cells. J South Med Univ (Chin) 2014;34:1758–1762.

Cheng Y, He SQ, Zhu Y, Fan Q, Yang S, Chen R. Biejiajian Pill inhibited the proliferation, adhesion, and invasion of hepatoma carcinoma cells: an experimental research. Chin J Integr Tradit West Mde (Chin) 2013;33:664–667.

Sun H, He S, Wen B, Jia W, Fan E, Zheng Y. Effect of Biejiajian Pills on Wnt signal pathway molecules β-catenin and GSK-3β and the target genes CD44v6 and VEGF in hepatocellular carcinoma cells. J South Med Univ (Chin) 2014;34:1454–1458.

Ai ZB, Zhang RH, Yan GH, Su YP, Ai GP. Effect of Modified Turtle shell Decoction on hepatic fibrosis in rats and its mechanism. Acta Acad Med Milit Tertiae (Chin) 2011;33:249–254.

He S, Cheng Y, Zhu Y, Fan Q, Sun H, Jia W. Effect of Biejiajian Pills on Wnt/β-catenin signal pathway and DKK-1 and FrpHe gene expressions in hepatocellular carcinoma cells. J South Med Univ (Chin) 2013;33:30–33.

Tang YP, Hu CL, Liu YW. Effect of bioactive peptide of Carapax Trionycis on TGF-β1-induced intracellular events in hepatic stellate cells. J Ethnopharmacol 2013;148:69–73.

Hu Z, You P, Xiong S, Gao J, Tang Y, Ye X, et al. Carapax Trionycis extracts inhibit fibrogenesis of activated hepatic stellate cells via TGF-β1/Smad and NFkB signaling. Biomed Pharmacother 2017;95:11–17.

Wang P, Zhang Y, An Y, Xu K, Xu X, Fu C, et al. Protection of a new heptapeptide from Carapax trionycis against carbon tetrachloride-induced acute liver injury in mice. Chem Pharm Bull (Tokyo) 2013;61:1130–1135.

Wen B, Sun HT, He SQ, An HY, Pang J. Inhibitory effect of Biejiajian pills on HepG2 cell xenograft growth an expression of β-catenin and Tbx3 in nude mice. J South Med Univ (Chin) 2016;36:210–214.

Yao L, Yao ZM, Yu T. Influence of BOL on hyaluronic acid, laminin and hyperplasia in hepatofibrotic rats. World J Gasteroenterol 2001;7:872–875.

Yao L, Yao ZM, Weng H, Zhao GP, Zhou YJ, Yu T. Effect of rat serum containing Biejiajian Oral Liquid on proliferation of rat hepatic stellate cells. World J Gastroenterol 2004;10:1911–1913.

Lee UE, Friedman SL. Mechanisms of hepatic fibrogenesis. Best Pract Res Clin Gastroenterol 2011;25:195–206.

Ghosh AK, Quaqqin SE, Vauqhan DE. Molecular basis of organ fibrosis: potential therapeutic approaches. Exp Biol Med 2013;238:461–481.

Grace JA, Herath CB, Mak KY, Burrell LM, Angus PW. Update on new aspects of the rennin-angiotensin system in liver disease: clinical implications and new therapeutic options. Clin Sci 2012;123:225–239.

Lu P, Liu HL, Yin H, Yang L. Expression of angiotensinogen during hepatic fibrogenesis and its effect on hepatic stellate cells. Med Sci Monit 2011;17: BR248–BR256.

Paik YH, Kim J, Aoyama T, De Mincicis S, Bataller R, Brenner DA. Role of NADPH oxidases in liver fibrosis. Antioxid Redox Signal 2014;20:2854–2872.

Yao ZM, Xiong YK, Li JP. Experimental study of resisting liver fibrosis of Biejiajian Oral Liquid. J Zhejiang Univ Tradit Chin Med (Chin) 2000;24:58–61.

Yao L, Zhang YL, Li J, Peng Y. Effect of Biejiajian Oral Liquid on the expression of RAAS in hepatic fibrosis rats. J Pharm Pharmacol 2012;3:330–335.

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