Tetramethylpyrazine attenuates carbon tetrachloride-caused liver injury and fibrogenesis and reduces hepatic angiogenesis in rats

被引：19

作者：

Zhao, Shifeng ^{[1
]}

Zhang, Zili ^{[1
]}

Qian, Linnan ^{[1
]}

Lin, Qiuyi ^{[1
]}

Zhang, Chenxi ^{[1
]}

Shao, Jiangjuan ^{[2
]}

Zhang, Feng ^{[1
,3
]}

Zheng, Shizhong ^{[1
,3
]}

机构：

[1] Nanjing Univ Chinese Med, Coll Pharm, Dept Pharmacol, 138 Xianlin Ave, Nanjing 210023, Jiangsu, Peoples R China

[2] Nanjing Univ Chinese Med, Coll Pharm, Dept Pharm, Nanjing 210023, Jiangsu, Peoples R China

[3] Nanjing Univ Chinese Med, Jiangsu Key Lab Pharmacol & Safety Evaluat Chines, Nanjing, Jiangsu, Peoples R China

来源：

BIOMEDICINE & PHARMACOTHERAPY | 2017年 / 86卷

基金：

中国国家自然科学基金;

关键词：

Liver fibrosis; Tetramethylpyrazine; Liver sinusoidal endothelial cell; Capillarization; Angiogenesis; Apoptosis; SINUSOIDAL ENDOTHELIAL-CELLS; GROWTH-FACTOR; STELLATE CELLS; FIBROSIS; EXPRESSION; PROGRESSION; RECEPTOR; PATHWAY;

D O I：

10.1016/j.biopha.2016.11.122

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Liver fibrosis represents a frequent event following chronic insult to trigger wound healing reactions with abnormalities of angiogenesis in the liver. Capillarization of liver sinusoidal endothelial cell (LSEC) is the pivotal event during liver angiogenesis. In the current study, we sought to investigate the effect of tetramethylpyrazine (TMP) on carbon tetrachloride (CCl4)-induced liver injury and fibrosis in rats, and to further examine the molecular mechanisms of TMP-induced anti-angiogenic effect. We found that TMP significantly ameliorated histopathological feature of liver fibrosis characterized by decreased collagen deposition, hepatocyte apoptosis, and expression of biochemical indicators, such as aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Moreover, TMP appeared to play an essential role in controlling pathological angiogenesis. In addition, TMP attenuated angiogenesis by downregulation of vascular endothelial growth factor-A (VEGF-A), vascular endothelial growth factor receptor 2 (VEGF-R2), platelet-derived growth factor-BB (PDGF-BB), and platelet-derived growth factor-beta receptor (PDGF-beta R), four important factors transmitting pro-angiogenic pathways. Besides, TMP inhibited LSEC capillarization in CCl4-induced liver fibrotic model with the morphological features of increasing sinusoidal fenestrae. Importantly, we found that disruption of angiogenesis is required for TMP to inhibit hepatocyte apoptosis in rats. Treatment with TMP significantly inhibited the expression of Bax, and up-regulated Bcl-2 expression. Interestingly, treatment with angiogenesis-inducer AngII dramatically eliminated the effect of TMP on Bax/Bcl-2 axis. Overall, these results provide novel perspectives to reveal the protective effect of TMP on liver, opening up the possibility of using TMP based anti-angiogenic drugs for the liver diseases. (C) 2016 Elsevier Masson SAS. All rights reserved.

引用

页码：521 / 530

页数：10

共 35 条

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