Institute of Cardiovascular Disease, Xuzhou Medical College, China.
Acta Pharmacol Sin. 2012 Jan;33(1):41-8. doi: 10.1038/aps.2011.133. Epub 2011 Nov 21.
To investigate the action of salvianolic acid A (SalA) on angiotensin II (Ang II)-induced proliferation of human umbilical vein endothelial cells (HUVECs) and the possible signaling pathways mediating this action.
Cell proliferation was examined with MTT assay. The expression levels of Src phosphorylation (phospho-Src), Akt phosphorylation (phospho-Akt), and NADPH oxidase 4 (Nox4) in HUVECs were determined by Western blot. The production of reactive oxygen species (ROS) was estimated using fluorescence-activated cell sorting (FACS).
SalA (6.25-50 μmol/L) did not affect the viability of HUVECs. Treatment of HUVECs with Ang II (1 μmol/L) markedly increased the cell viability; pretreatment of HUVECs with SalA (12.5, 25 and 50 μmol/L) prevented Ang II-induced increase of the cell viability in a concentration-dependent manner. Treatment of HUVECs with Ang II (1 μmol/L) markedly up-regulated the protein expression levels of phospho-Src, phospho-Akt (473) and Nox4; pretreatment of HUVECs with SalA (12.5, 25 and 50 μmol/L) blocked all the effects in a concentration-dependent manner. Treatment of HUVECs with Ang II (1 μmol/L) dramatically increased ROS production in HUVECs; pretreatment of HUVECs with SalA (12.5, 25 and 50 μmol/L) blocked the ROS production in a concentration-dependent manner.
SalA inhibits Ang II-induced proliferation of HUVECs via reducing the expression levels of phospho-Src and phospho-Akt (473), thereby attenuating the production of ROS.
研究丹酚酸 A（SalA）对血管紧张素 II（Ang II）诱导的人脐静脉内皮细胞（HUVEC）增殖的作用及可能的信号转导途径。
用 MTT 法检测细胞增殖。Western blot 法测定 HUVEC 中Src 磷酸化（phospho-Src）、Akt 磷酸化（phospho-Akt）和 NADPH 氧化酶 4（Nox4）的表达水平。用流式细胞术（FACS）测定活性氧（ROS）的产生。
SalA（6.25-50 μmol/L）不影响 HUVEC 的活力。用 Ang II（1 μmol/L）处理 HUVEC 可显著增加细胞活力；用 SalA（12.5、25 和 50 μmol/L）预处理 HUVEC 可浓度依赖性地阻止 Ang II 诱导的细胞活力增加。用 Ang II（1 μmol/L）处理 HUVEC 可显著上调 phospho-Src、phospho-Akt（473）和 Nox4 的蛋白表达水平；SalA（12.5、25 和 50 μmol/L）预处理可浓度依赖性地阻断所有这些作用。用 Ang II（1 μmol/L）处理 HUVEC 可显著增加 HUVEC 中的 ROS 产生；SalA（12.5、25 和 50 μmol/L）预处理可浓度依赖性地阻断 ROS 的产生。
SalA 通过降低 phospho-Src 和 phospho-Akt（473）的表达水平，抑制 Ang II 诱导的 HUVEC 增殖，从而减少 ROS 的产生。
