上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（基础研究） • 上一篇    下一篇

二甲双胍对TNF-α诱导的血管平滑肌细胞增殖及炎症反应的影响

张多多，李 湃，张 微，孔晶晶，秦 宇，魏春阳   

  1. 大连医科大学附属第一医院特需医疗科， 大连 116011
  • 出版日期:2014-09-28 发布日期:2014-09-26
  • 通讯作者: 魏春阳, 电子信箱: cywei@126.com。
  • 作者简介:张多多(1977—)， 女， 主治医师, 硕士生; 电子信箱: drzhang5@163.com。

Effects of metformin on proliferation and inflammatory response of vascular smooth muscle cells induced by TNF-α

ZHANG Duo-duo, LI Pai, ZHANG Wei, KONG Jing-jing, QIN Yu, WEI Chun-yang   

  1. Department of Special Medical Branch, the First Hospital Affiliated to Dalian Medical University， Dalian 116011， China
  • Online:2014-09-28 Published:2014-09-26

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摘要：

目的 探讨二甲双胍对肿瘤坏死因子-α （TNF-α）诱导的血管平滑肌细胞（VSMCs）增殖及炎症反应的影响及可能机制。方法 以不同浓度TNF-α和二甲双胍处理VSMCs 24 h，MTT比色法筛选最适处理浓度，在此基础上将细胞分为对照组、TNF-α组、TNF-α+二甲双胍组和二甲双胍组，采用流式细胞术检测细胞周期，RT-PCR、Western blotting检测环氧化酶-2 (COX-2)和诱导型一氧化氮合酶(iNOS)的表达，Western blotting检测AMPK以及磷酸化AMPK（p-AMPK）的表达。结果 10 ng/mL TNF-α处理组的吸光度值显著增高（P<0.01），加入2 mmol/L二甲双胍孵育后的吸光度值变化最为明显（P<0.05）。在二甲双胍+TNF-α组，G1期细胞比率明显低于对照组而高于TNF-α组；细胞iNOS和Cox-2的表达减少，p-MAPK表达增加。结论 二甲双胍可能通过AMPK途径阻滞细胞周期，抑制TNF-α诱导的VSMCs增殖及炎症反应。

关键词: 二甲双胍, 肿瘤坏死因子-α, 血管平滑肌细胞

Abstract:

Objective To investigate the effects of metformin on the proliferation and inflammatory response of vascular smooth muscle cells (VSMCs) induced by tumor necrosis factor-α (TNF-α) and their possible mechanisms. Methods VSMCs were treated by TNF-α and metformin of different concentrations for 24 h. Concentrations that were most suitable for treatment were selected by the MTT, and VSMCs were divided into the control group, TNF-α group, TNF-α+metformin group, and metformin group. The cell cycle was detected by the flow cytometry. Expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were detected by the RT-PCR and Western blotting. Expressions of AMPK and p-AMPK were detected by the Western blotting. Results The absorbance value of the group treated by TNF-α of 10 ng/mL significantly increased (P<0.01). The variation of absorbance value of the group treated by metformin of 2 mmol/L was the most significant (P<0.05). The cell rate of G1 phase of the TNF-α+metformin group was significantly lower than that of the control group and higher than that of the TNF-α group. The expressions of iNOS and COX-2 decreased and the expression of p-AMPK increased. Conclusion Metformin can arrest the cell cycle and inhibit the proliferation and inflammatory response of VSMCs induced by TNF-α through activating the AMPK signaling pathway.

Key words: metformin, tumor necrosis factor-α, vascular smooth muscle cell