论著(基础研究)

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 ,
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  • 大连医科大学附属第一医院特需医疗科, 大连 116011
张多多(1977—), 女, 主治医师, 硕士生; 电子信箱: drzhang5@163.com。

网络出版日期: 2014-09-26

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

  • ZHANG Duo-duo ,
  • LI Pai ,
  • ZHANG Wei ,
  • et al
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  • Department of Special Medical Branch, the First Hospital Affiliated to Dalian Medical University, Dalian 116011, China

Online published: 2014-09-26

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。

本文引用格式

张多多 , 李 湃 , 张 微 , . 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[J]. 上海交通大学学报(医学版), 2014 , 34(9) : 1343 . DOI: 10.3969/j.issn.1674-8115.2014.09.017

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.

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