sirtuin-1在肺泡巨噬细胞金属基质蛋白酶9表达中作用

发布时间：2019-03-30 16:17

【摘要】：目的:肺泡巨噬细胞(alveolar macrophages,AM)的金属基质蛋白酶9(matrix metalloproteinases 9,MMP9)表达在慢性阻塞性肺病(chronic obstructive pulmonary disease,COPD)及肺气肿形成中起重要作用,但该细胞对于MMP9表达调控机制尚不明确。本研究就NAD依赖性蛋白脱乙酰酶sirtuin-1(Sirt1)在MMP9表达调控中的可能作用开展研究。方法:体外培养小鼠AM,建立香烟烟雾提取物(cigarette smoking extract,CSE)刺激模型;观察加入Sirt1激动剂白藜芦醇后的细胞内MMP9表达量变化;建立Sirt1基因siRNA干扰模型,观察Sirt1基因被抑制后的AM胞内MMP9表达状况。结果:1%CSE刺激后AM胞内MMP9表达明显增加(P0.05),此作用可被Sirt1激动剂白藜芦醇所拮抗,其拮抗效应呈浓度依赖性;采用siRNA干扰AM细胞Sirt1基因表达后,AM细胞内MMP9表达明显增加(P0.05)。结论:Sirt1参与了AM细胞对MMP9的表达调控作用,其可能在COPD的发生发展中起保护性作用。
[Abstract]:Objective: the expression of matrix metalloproteinase 9 (matrix metalloproteinases 9 (MMP 9) in alveolar macrophages (alveolar macrophages,AM) plays an important role in the formation of chronic obstructive pulmonary disease (chronic obstructive pulmonary disease,COPD) and emphysema. However, the mechanism of the regulation of MMP9 expression by this cell is not clear. In this study, we investigated the possible role of NAD-dependent protein deacetylase sirtuin-1 (Sirt1) in the regulation of MMP9 expression. Methods: the model of cigarette smoke extract (cigarette smoking extract,CSE) stimulation was established by in vitro culture of mouse AM, and the changes of intracellular MMP9 expression were observed after Sirt1 agonist resveratrol was added. The siRNA interference model of Sirt1 gene was established to observe the expression of MMP9 in AM after Sirt1 gene was inhibited. Results: the expression of MMP9 in AM was significantly increased after 1%CSE stimulation (P0.05), which could be antagonized by resveratrol, a Sirt1 agonist, in a concentration-dependent manner. After siRNA interfered with the expression of Sirt1 gene in AM cells, the expression of MMP9 in AM cells increased significantly (P0.05). Conclusion: Sirt1 is involved in the regulation of MMP9 expression in AM cells, which may play a protective role in the genesis and development of COPD.
【作者单位】：南京医科大学第一附属医院呼吸科;
【基金】：国家自然科学基金资助(81070025)
【分类号】：R563.9

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