- 期刊
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
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肌細胞增生有關。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（心效痛或心肌梗塞引起）。本研說明，此方具有抗血管不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硬化疾病。
關鍵字
無資料並列摘要
Background 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 regulaion 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一inducible cell cycle progression at the Gl/S phase. Further experiments indicated that the two cGMP – elevating agents primarily blocked theactivation 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 Rαs - dependent activation of Raf - 1.