Protective Effect of Ganshuang Granules (肝爽颗粒) on Liver Cirrhosis by Suppressing Regulatory T Cells in Mouse Model

Yan-min LIU; Hong-bo SHI; Yi-rong LIU; Hong-lin SHI; Feng REN; Yu CHEN; De-xi CHEN; Jin-li LOU; Zhong-ping DUAN

doi:10.1007/s11655-015-2430-9

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Protective Effect of Ganshuang Granules (肝爽颗粒) on Liver Cirrhosis by Suppressing Regulatory T Cells in Mouse Model

Original Article | Updated：2021-08-27

- Protective Effect of Ganshuang Granules (肝爽颗粒) on Liver Cirrhosis by Suppressing Regulatory T Cells in Mouse Model
- Protective Effect of Ganshuang Granules (肝爽颗粒) on Liver Cirrhosis by Suppressing Regulatory T Cells in Mouse Model
- Chinese Journal of Integrative Medicine 2019年25卷第1期页码：51-58
- Affiliations：
  
  1.Department of Liver Diseases Immunology, Beijing Youan Hospital, Capital Medical University, Beijing (100069), China
  2.Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing (100069), China
  3.Department of Toxic Hepatic Disease, Beijing Youan Hospital, Capital Medical University, Beijing (100069), China
  4.Artifical Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing (100069), China
  5.Clinical Laboratory Center, Beijing Youan Hospital, Capital Medical University, Beijing (100069), China
- Author bio：
  
  Correspondence to: Dr. DUAN Zhong-ping, Tel: 86-10-63291007, E-mail: duan2517@163.com
- Funds：
  
  the China National Key Project of Twelfth Five-Year Plan(2012ZX10002004-006;2012ZX10004904-003-001;2013ZX10002002-006-001);National Natural Science Foundation of China(81300349);Beijing Natural Science Foundation(7144216);Beijing Nova Program(Z131107000413016);Project of Science and Technology Activities Preferred Overseas Personnel of Beijing(2014)
- DOI：10.1007/s11655-015-2430-9
  中图分类号：
- 纸质出版日期：2019-01-01，
  
  网络出版日期：2015-11-05，
  
  录用日期：2015-04-10
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Yan-min LIU, Hong-bo SHI, Yi-rong LIU, 等. Protective Effect of Ganshuang Granules (肝爽颗粒) on Liver Cirrhosis by Suppressing Regulatory T Cells in Mouse Model[J]. Chinese Journal of Integrative Medicine, 2019,25(1):51-58.

Yan-min LIU, Hong-bo SHI, Yi-rong LIU, et al. Protective Effect of Ganshuang Granules (肝爽颗粒) on Liver Cirrhosis by Suppressing Regulatory T Cells in Mouse Model[J]. Chinese Journal of Integrative Medicine, 2019,25(1):51-58.
Yan-min LIU, Hong-bo SHI, Yi-rong LIU, 等. Protective Effect of Ganshuang Granules (肝爽颗粒) on Liver Cirrhosis by Suppressing Regulatory T Cells in Mouse Model[J]. Chinese Journal of Integrative Medicine, 2019,25(1):51-58. DOI： 10.1007/s11655-015-2430-9.

Yan-min LIU, Hong-bo SHI, Yi-rong LIU, et al. Protective Effect of Ganshuang Granules (肝爽颗粒) on Liver Cirrhosis by Suppressing Regulatory T Cells in Mouse Model[J]. Chinese Journal of Integrative Medicine, 2019,25(1):51-58. DOI： 10.1007/s11655-015-2430-9.

摘要

Abstract

Objective:

To investigate the potential antifibrotic mechanisms of Chinese medicine Ganshuang Granules (肝爽颗粒

GSG) and to provide clinical therapeutic evidence of its effects.

Methods:

A cirrhotic mouse model was established by intraperitoneally injecting a mixture of CCl

(40%) and oil (60%) at 0.2 mL per 100 g of body weight twice a week for 12 weeks. After 12-week modeling

GSG was intragastric administrated to the mice for 2 weeks

and the mice were divided into low-

medium- and high-dose groups at doses of 1

2 and 4 g/(kg•day)

respectively. Liver morphology changes were observed using Masson's trichrome staining and B-ultrasound. The levels of alanine aminotransferase (ALT)

aspartate aminotransferase (AST) and hyaluronic acid (HA) in serum were detected using an automatic biochemistry analyzer. The expressions of desmin

smooth muscle actin (SMA) and Foxp3 in liver were detected by immunofluorescence. The regulatory T cell (Treg) frequency was determined through flow cytometry analysis. Collagen-Ⅰ

SMA

IL-6

tumor necrosis factor α (TNF-α)

interleukin (IL)-1β and transforming growth factor β1 (TGF-β1) expression levels were measured using quantitative polymerase chain reaction (qPCR).

Results:

Masson's staining result showed fewer pseudolobule structures and fibrous connective tissue in the GSG-treatment groups than in the spontaneous recovery group. Ultrasonography showed that GSG treatment reduced the number of punctate hyperechoic lesions in mice cirrhotic livers. The serum ALT

AST

HA levels were significantly ameliorated by GSG treatment (ALT:

=8.104

=0.000; AST:

=7.078

=0.002; and HA:

=7.621

=0.001). The expression levels of collagen-Ⅰ and SMA in the cirrhotic livers were also attenuated by GSG treatment (collagen-Ⅰ:

=3.938

=0.011; SMA:

=4.115

=0.009). Tregs

which were elevated in the fibrotic livers

were suppressed by GSG treatment (

=8.268

=0.001). The expressions of IL-6

TNF-α and IL-1β increased

and TGF-β levels decreased in the cirrhotic livers after GSG treatment (IL-6:

=5.457

=0.004; TNF-α:

=6.023

=0.002; IL-1β:

=6.658

=0.001; and TGF-β1:

=11.239

=0.000).

Conclusions:

GSG promoted the resolution/regression of cirrhosis and restored liver functions in part by suppressing Treg cell differentiation

which may be mediated by hepatic stellate cells.

关键词

Keywords

Ganshuang Granulesliver cirrhosisregulatory T cellhepatic stellate cellChinese medicine

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