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題名 | 血府逐瘀湯經由抑制上皮細胞生長因子訊號傳遞路徑來抑制血管平滑肌細胞增生之分子機轉=Xue-Fu-Zhu-Yu-Tang (XFZYT) Suppress Proliferation of Vascular Smooth Muscle Cells by Inhibiting the Activation of Epidermal Growth Factor Signaling Pathway |
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作者 | 余淑美; Yu, Shu-mei; |
期刊 | 臺灣中醫醫學雜誌 |
出版日期 | 20020300 |
卷期 | 1:2 2002.03[民91.03] |
頁次 | 頁58-76 |
分類號 | 414.5 |
語文 | chi |
關鍵詞 | 血府逐瘀湯; 血管平滑肌細胞增生; 冠心疾病; |
中文摘要 | 冠心疾病是國人最常見的心血管疾病之一,其病理機轉與不正常血小 板凝集,血管痙攣及血管平滑細胞增生有關。其中廣泛性血管平滑肌細胞增生將 是引起粥狀動脈硬化症中最主要的一個病理因素。血府逐瘀湯主要功效為活血化 瘀,主治胸痛(心絞痛或心肌梗塞引起)。本研究說明,此方具有抗血管平滑肌 細胞增生的作用,其分子機轉是經由增加cGMP/PKG來干擾上皮細胞生長因子 (epidermal growth factor, EGF)的訊號傳遞路徑Ras-dependent Raf-1 Kinase活 化,來參與抑制平滑肌細胞的增生,此項作用可用於預防冠心疾病等血管粥狀動 脈礎化疾病。 |
英文摘要 | Backgruond Abnormal proliferation of vascular smooth muscle cells (VSMC) is a key event in the pathogenesis of atherosclerosis and many vascular diseases. It is known that nitric oxide released from the endothelium participates in the regulation of VSMC proliferation via a cyclic 3' , 5' – guanosine monophosphate (cGMP)-mediated mechanism. In a series of experiments, sodium nitroprusside (SNP) and XFZYT were evaluated for their antiproliferative effect and the mechanism of their cGMP-elevating action. Methods and Results The effect of SNP and XFZYT on epidermal growth factor (EGF)-stimulated proliferation of rat aortic smooth muscle cells (VSMC) was examined. Cell proliferation was measured in terms of [3H] thymidine incorporation, flow cytometry, and the cell number. Further, their effect on the EGF-activated signal transduction pathway was assessed by measuring mitogen-activated protein kinases (MAPK), MAPK kinase (MEK), Raf-1 activity, and the formation of active form of Ras. SNP and XFZYT inhibited EGF-induced DNA synthesis and subsequent proliferation of VSMC. These two increased cGMP but only a little cAMP in VSMC. A similar antiproliferative effect was observed with 8-bromo-cGMP. The antiproliferative effect of the two was reversed by KT5823 but not by dideoxyadenosine nor Rp-cAMPS. SNP and XFZYT blocked the EGF-inducible cell cycle progression at the G1/S phase. Further experiments indicated that the two cGMP-elevating agents primarily blocked the activation of Raf-1 by EGF-activated Ras. Conclusions These results demonstrate that cGMP-elevating agents inhibit [3H] thymidine incorporation and thus the growth of VSMC, and this inhibition appears to attenuate EGF-activated signal transduction pathway by preventing Ras-dependent activation of Raf-1. |
本系統之摘要資訊系依該期刊論文摘要之資訊為主。