Xiayuxue Decoction (下瘀血汤) attenuates hepatic stellate cell activation and sinusoidal endothelium defenestration in CCl4-induced fibrotic liver of mice

Li-jun Zhang; Ming-yu Sun; Bing-bing Ning; Wen-meng Zhang; Gao-feng Chen; Yong-ping Mu; Hua Zhang; Jia Liu; Yan-qin Bian; Ping Liu

doi:10.1007/s11655-014-1862-y

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Xiayuxue Decoction (下瘀血汤) attenuates hepatic stellate cell activation and sinusoidal endothelium defenestration in CCl4-induced fibrotic liver of mice

Updated：2021-08-27

- Xiayuxue Decoction (下瘀血汤) attenuates hepatic stellate cell activation and sinusoidal endothelium defenestration in CCl4-induced fibrotic liver of mice
- Chinese Journal of Integrative Medicine Vol. 20, Issue 7, Pages: 516-523(2014)
- Affiliations：
  
  1. Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai,China
  2. Institute of Traditional Chinese Internal Medicine, Shanghai Municipal Education Commission, Shanghai,E,China
  3. Key Laboratory of Liver and Kidney Diseases, Shanghai University of Traditional Chinese Medicine,Shanghai,China
- Author bio：
- Funds：
  
  Supported by China Postdoctoral Science Foundation funded project (No. 20110490750), Shanghai Leading Academic Discipline Project (No. Y0302), E-institute of Shanghai Municipal Education Commission (No. E03008), Innovative Research Team in Universities, Shanghai Municipal Education Commission, Key Disciplines of Liver and Gallbladder Diseases and Key Laboratory of Chronic Liver Disease of State Administration of Traditional Chinese Medicine of China, National Basic Research Program of China (No. 2006CB504801), National S&T Major Project (No. 2009ZX09311-003)
- DOI：10.1007/s11655-014-1862-y
  CLC：
- Published：2014，
  
  Published Online：28 June 2014，
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Zhang, Lj., Sun, My., Ning, Bb. et al. Xiayuxue Decoction (下瘀血汤) attenuates hepatic stellate cell activation and sinusoidal endothelium defenestration in CCl4-induced fibrotic liver of mice., Chin. J. Integr. Med. 20, 516–523 (2014). https://doi.org/10.1007/s11655-014-1862-y

Li-jun Zhang, Ming-yu Sun, Bing-bing Ning, et al. Xiayuxue Decoction (下瘀血汤) attenuates hepatic stellate cell activation and sinusoidal endothelium defenestration in CCl4-induced fibrotic liver of mice. [J]. Chinese Journal of Integrative Medicine 20(7):516-523(2014)
Zhang, Lj., Sun, My., Ning, Bb. et al. Xiayuxue Decoction (下瘀血汤) attenuates hepatic stellate cell activation and sinusoidal endothelium defenestration in CCl4-induced fibrotic liver of mice., Chin. J. Integr. Med. 20, 516–523 (2014). https://doi.org/10.1007/s11655-014-1862-y DOI：

Li-jun Zhang, Ming-yu Sun, Bing-bing Ning, et al. Xiayuxue Decoction (下瘀血汤) attenuates hepatic stellate cell activation and sinusoidal endothelium defenestration in CCl4-induced fibrotic liver of mice. [J]. Chinese Journal of Integrative Medicine 20(7):516-523(2014) DOI： 10.1007/s11655-014-1862-y.

摘要

To investigate the effects of ancient Chinese medical formula Xiayuxue Decoction (下瘀血汤

XYXD) on activation of hepatic stellate cells (HSCs) and defenestration of sinusoidal endothelial cells (SECs) in CCl4-induced fibrotic liver of mice. High performance liquid chromatography was used to identify the main components of XYXD and control the quality of extraction. C57BL/6 mice were induced liver fibrosis by CCl4 exposure and administered with XYXD for 6 weeks simultaneously. Liver tissue was investigated by hematoxylin-eosin and Sirius-red staining. Sinusoidal fenestrations were observed by scanning electronic microscopy and fluorescent immunohistochemistry of PECAM-1 (CD31). Whole liver lysates were detected of α-smooth muscle actin (α-SMA) and type-I collagen by Western blot. Primary rat HSCs-T6 cells were analyzed by detecting α-SMA

F-actin

DNA fragmentation through confocal microscopy

Western blot

terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay and cellomics arrayscan

respectively. Amygdalin and emodin in XYXD were identified. XYXD (993 mg/kg) inhibited Sirius red positive area up to 70.1% (P<0.01)

as well as protein levels of α-SMA and type-I collagen by 42.0% and 18.5% (P<0.05) respectively. In vitro

XYXD (12.5 μg/mL

50 μg/mL) suppressed the activation of HSCs and reversed the myofibroblastic HSCs into quiescent

demonstrated as inhibition of fluorescent F-actin by 32.3% and 46.6% (P<0.05). Besides

XYXD induced the apoptosis of HSC-T6 cells by 20.0% (P<0.05) and 49.5% (P<0.01)

evidenced by enhanced TUNEL positivity. Moreover

ultrastructural observation suggested XYXD inhibited defenestration of SECs

which was confirmed by 31.1% reduction of protein level of CD31 (P<0.05). XYXD inhibited both HSCs activation and SECs defenestration which accompany chronic liver injuries. These data may help to understand the underlying mechanisms of XYXD for prevetion of chronic liver diseases.

Abstract

To investigate the effects of ancient Chinese medical formula Xiayuxue Decoction (下瘀血汤

F-actin

DNA fragmentation through confocal microscopy

Western blot

terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay and cellomics arrayscan

respectively. Amygdalin and emodin in XYXD were identified. XYXD (993 mg/kg) inhibited Sirius red positive area up to 70.1% (P<0.01)

as well as protein levels of α-SMA and type-I collagen by 42.0% and 18.5% (P<0.05) respectively. In vitro

XYXD (12.5 μg/mL

50 μg/mL) suppressed the activation of HSCs and reversed the myofibroblastic HSCs into quiescent

demonstrated as inhibition of fluorescent F-actin by 32.3% and 46.6% (P<0.05). Besides

XYXD induced the apoptosis of HSC-T6 cells by 20.0% (P<0.05) and 49.5% (P<0.01)

evidenced by enhanced TUNEL positivity. Moreover

ultrastructural observation suggested XYXD inhibited defenestration of SECs

关键词

Liver Fibrosiscirrhosishepatic stellate cellliver sinusoidal endothelial cellXiayuxue Decoction

Keywords

Liver Fibrosiscirrhosishepatic stellate cellliver sinusoidal endothelial cellXiayuxue Decoction

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Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Institute of Liver Diseases, Shanghai University of Chinese medicine

Department of Gastroenterology, Shanghai East Hospital Affiliated to Tongji University

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