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田基黄苷对血管紧张素II诱导的大鼠血管平滑肌细胞增殖、迁移及TGF-β/Smad信号通路的影响

Effects of Tilianin on Proliferation, Migration and TGF-β/Smad Signaling in Rat Vascular Smooth Muscle Cells Induced with Angiotensin II.

作者信息

Cao Wenjiang, Hu Na, Yuan Yong, Cheng Jiang, Guo Xinhong, Wang Yanfang, Wang Xinchun, Hu Ping

机构信息

First Affiliated Hospital of the Medical College, Shihezi University, Xinjiang, 832008, China.

College of Medicine, Shihezi University, Xinjiang, 832002, China.

出版信息

Phytother Res. 2017 Aug;31(8):1240-1248. doi: 10.1002/ptr.5846. Epub 2017 Jun 16.

DOI:10.1002/ptr.5846
PMID:28620995
Abstract

Flavonoid Tilianin was isolated from Dracocephalum moldavica, and its pharmacological mechanism on proliferation, migration and the TGF-β/Smad signaling pathway in rat vascular smooth muscle cells (VSMCs) induced with Angiotensin II (Ang II) was systematically evaluated. Primary rat VSMCs were stimulated with Ang II to induce proliferation. The cells were then treated with Tilianin for 24 or 48 h. MTT assay and Transwell assays were used to evaluate the effects of Tilianin on proliferation and migration. The expression of intracellular proliferating cell nuclear antigen (PCNA), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were measured by immunohistochemistry as verification of effects on proliferation and migration. The expression of TGF-β1, Smad2 and Smad3 mRNA was measured by qRT-PCR, and the expression of TGF-β1 and P-Smad2/3 protein was measured by Western blotting. The results show that Tilianin can inhibit proliferation and expression of intracellular PCNA in VSMCs induced with Ang II, in a dose-dependent manner. Tilianin also mediates a dose-dependent inhibition of migration and the expression of intracellular ICAM-1, VCAM-1, MMP-2 and MMP-9. Furthermore, TGF-β1, Smad2, Smad3, Smad2/3 and P-Smad2/3 in Ang II-induced VSMCs are suppressed by Tilianin. The inhibitory effects of Tilianin support its use in the suppression and treatment of atherosclerosis. Copyright © 2017 John Wiley & Sons, Ltd.

摘要

从香青兰中分离出黄酮类化合物田蓟苷,并系统评估了其对血管紧张素 II(Ang II)诱导的大鼠血管平滑肌细胞(VSMCs)增殖、迁移及 TGF-β/Smad 信号通路的药理机制。用 Ang II 刺激原代大鼠 VSMCs 以诱导增殖。然后用田蓟苷处理细胞 24 或 48 小时。采用 MTT 法和 Transwell 法评估田蓟苷对增殖和迁移的影响。通过免疫组织化学检测细胞内增殖细胞核抗原(PCNA)、细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子-1(VCAM-1)的表达,以验证其对增殖和迁移的影响。通过 qRT-PCR 检测 TGF-β1、Smad2 和 Smad3 mRNA 的表达,通过 Western blotting 检测 TGF-β1 和 P-Smad2/3 蛋白的表达。结果表明,田蓟苷可剂量依赖性地抑制 Ang II 诱导的 VSMCs 增殖及细胞内 PCNA 的表达。田蓟苷还可剂量依赖性地抑制迁移以及细胞内 ICAM-1、VCAM-1、MMP-2 和 MMP-9 的表达。此外,田蓟苷可抑制 Ang II 诱导的 VSMCs 中 TGF-β1、Smad2、Smad3、Smad2/3 和 P-Smad2/3 的表达。田蓟苷的抑制作用支持其用于动脉粥样硬化的抑制和治疗。版权所有©2017 约翰威立父子有限公司。

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