Inhibition of Angiogenesis, Fibrosis and Thrombosis by Tetramethylpyrazine: Mechanisms Contributing to the SDF-1/CXCR4 Axis

被引：82

作者：

Cai, Xiaoxiao ^{[1
]}

Chen, Zhao ^{[1
]}

Pan, Xueke ^{[1
]}

Xia, Lei ^{[1
]}

Chen, Pei ^{[1
]}

Yang, Ying ^{[1
]}

Hu, Huan ^{[1
]}

Zhang, Jing ^{[1
]}

Li, Kaijing ^{[1
]}

Ge, Jian ^{[1
]}

Yu, Keming ^{[1
]}

Zhuang, Jing ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China

来源：

PLOS ONE | 2014年 / 9卷 / 02期

关键词：

CIRCULATING FIBROCYTES; CHEMOKINE RECEPTOR; GLIOMA-CELLS; CXCR4; ACTIVATION; PROMOTES;

D O I：

10.1371/journal.pone.0088176

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Background: Tetramethylpyrazine (TMP) is one of the active ingredients extracted from the Chinese herb Chuanxiong, which has been used to treat cerebrovascular and cardiovascular diseases, pulmonary diseases and cancer. However, the molecular mechanisms underlying the actions of TMP have not been fully elucidated. In a previous study we showed that TMP-mediated glioma suppression and neural protection involves the inhibition of CXCR4 expression. The SDF-1/CXCR4 axis plays a fundamental role in many physiological and pathological processes. In this study, we further investigated whether the regulation of the SDF-1/CXCR4 pathway is also involved in the TMP-mediated inhibition of neovascularization or fibrosis and improvement of microcirculation. Methodology/Principal Findings: Using a scratch-wound assay, we demonstrated that TMP significantly suppressed the migration and tubule formation of the human umbilical vein endothelial cell line ECV304 in vitro. The expression of CXCR4 in ECV304 cells is notably down-regulated after TMP treatment. In addition, TMP significantly suppresses corneal neovascularization in a rat model of corneal alkali burn injury. The expression of CXCR4 on days 1, 3 and 7 post-injury was determined through RT-PCR analysis. Consistent with our hypotheses, the expression of CXCR4 in the rat cornea is significantly increased with alkali burn and dramatically down-regulated with TMP treatment. Moreover, TMP treatment significantly attenuates bleomycin-induced rat pulmonary fibrosis, while immunofluorescence shows a notably decreased amount of CXCR4-positive cells in the TMP-treated group. Furthermore, TMP significantly down-regulates the expression of CXCR4 in platelets, lymphocytes and red blood cells. Whole-blood viscosity and platelet aggregation in rats are significantly decreased by TMP treatment. Conclusions: These results show that TMP exerts potent effects in inhibiting neovascularization, fibrosis and thrombosis under pathological conditions; thus, the underlying mechanism of TMP might partially contribute to the down-regulation of CXCR4.

引用

页数：9

共 43 条

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CIRCULATING FIBROCYTES DEFINE A NEW LEUKOCYTE SUBPOPULATION THAT MEDIATES TISSUE-REPAIR [J].