Inhibition of angiogenesis, fibrosis and thrombosis by tetramethylpyrazine: mechanisms contributing to the SDF-1/CXCR4 axis.
Inhibition of angiogenesis, fibrosis and thrombosis by tetramethylpyrazine: mechanisms contributing to the SDF-1/CXCR4 axis.
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四甲基吡嗪抑制血管生成、纤维化和血栓形成：影响 SDF-1/CXCR4 轴的机制
DOI：
10.1371/journal.pone.0088176
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zhuang J
中科院分区：
文献类型：
--
作者：
Cai X;Chen Z;Pan X;Xia L;Chen P;Yang Y;Hu H;Zhang J;Li K;Ge J;Yu K;Zhuang J
研究背景川芎嗪（Tetramethylpyrazine，TMP）是从中药甘草中提取的有效成分之一，用于治疗心脑血管疾病、肺部疾病和癌症。然而，TMP作用的分子机制尚未完全阐明。在先前的研究中，我们发现TMP介导的胶质瘤抑制和神经保护涉及CXCR 4表达的抑制。SDF-1/CXCR 4轴在许多生理和病理过程中起着重要作用。在这项研究中，我们进一步研究了SDF-1/CXCR 4通路的调节是否也参与TMP介导的抑制新生血管或纤维化以及改善微循环。方法/主要发现使用划痕试验，我们证明，TMP显着抑制迁移和微管形成的人脐静脉内皮细胞系ECV 304在体外。TMP处理后ECV 304细胞CXCR 4表达明显下调。此外，在角膜碱烧伤大鼠模型中，TMP显著抑制角膜新生血管形成。RT-PCR检测CXCR 4在伤后第1、3、7天的表达。与我们的假设一致，大鼠角膜中CXCR 4的表达在碱烧伤时显著增加，而在TMP治疗时显著下调。此外，TMP治疗显著减弱博莱霉素诱导的大鼠肺纤维化，而免疫荧光显示TMP治疗组中CXCR 4阳性细胞的量显著减少。此外，TMP显著下调血小板、淋巴细胞和红细胞中CXCR 4的表达。川芎嗪能显著降低大鼠全血粘度和血小板聚集率。结论TMP对病理状态下的新生血管、纤维化和血栓形成有明显的抑制作用，其机制可能与下调CXCR 4有关。
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.
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影响因子：
15.9
作者：
Fu, Yu-Show;Lin, Yen-Yang;Wang, Jia-Yi
通讯作者：
Wang, Jia-Yi
影响因子：
20.3
作者：
Kowalska, MA;Ratajczak, MZ;Poncz, M
通讯作者：
Poncz, M
影响因子：
0.7
作者：
Makino, Hideki;Aono, Yoshinori;Nishioka, Yasuhiko
通讯作者：
Nishioka, Yasuhiko
四甲基吡嗪（TMP）通过下调趋化因子受体CXCR4表达保护脑神经细胞并抑制胶质瘤
影响因子：
9.7
作者：
Chen, Zhao;Pan, Xueke;Zhuang, Jing
通讯作者：
Zhuang, Jing
影响因子：
15.9
作者：
Phillips, RJ;Burdick, MD;Strieter, RM
通讯作者：
Strieter, RM