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

Autor: Feng Zhang, Shifeng Zhao, Linnan Qian, Chenxi Zhang, Shizhong Zheng, Qiuyi Lin, Zili Zhang, Jiangjuan Shao
Rok vydání: 2017
Předmět:
Liver Cirrhosis
Male
Vascular Endothelial Growth Factor A
0301 basic medicine
Pathology
medicine.medical_specialty
Angiogenesis
medicine.medical_treatment
Becaplermin
Down-Regulation
Angiogenesis Inhibitors
Apoptosis
Biology
Pharmacology
urologic and male genital diseases
Rats
Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
Fibrosis
medicine
Animals
Tetramethylpyrazine
Receptors
Platelet-Derived Growth Factor
Carbon Tetrachloride
bcl-2-Associated X Protein
Liver injury
Neovascularization
Pathologic
Growth factor
Endothelial Cells
Kinase insert domain receptor
Proto-Oncogene Proteins c-sis
General Medicine
medicine.disease
Vascular Endothelial Growth Factor Receptor-2
Rats
Up-Regulation
Endothelial stem cell
030104 developmental biology
Liver
Proto-Oncogene Proteins c-bcl-2
chemistry
Pyrazines
Hepatocytes
Wound healing
Zdroj: Biomedicine & Pharmacotherapy. 86:521-530
ISSN: 0753-3322
DOI: 10.1016/j.biopha.2016.11.122
Popis: 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-β receptor (PDGF-βR), 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.
Databáze: OpenAIRE
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