sirtuin-1在肺泡巨噬细胞金属基质蛋白酶9表达中作用
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国家自然科学基金资助(81070025)


Role of sirtuin1 in matrix metalloproteinases 9(MMP-9)expression in alveolar macrophages
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    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(P < 0.05),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(P < 0.05)-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:Metalloproteinases 9(MMP-9)of alveolar macrophages(AM)has been shown to play an important role in the formation of chronic obstructive pulmonary disease(COPD) and emphysema. However,its effect on expression and regulation mechanism is still not clear. This study is aimed to investigate the potential role of sirtuin1(Sirt1)in the expression and regulation mechanism of matrix metalloproteinases 9(MMP-9)in alveolar macrophages(AM). Methods:The AMs were cultured in rats,the simulation model was established using cigarette smoking extract(CSE). To observe change of expression of MM9 in cells. The interference model was established using siRNA to observe expression of MMP-9 after the inhibition of Sirt1. Results:MMP-9 expression increased significantly(P < 0.05)due to 1% CSE stimulation. However,this effect can be antagonized by the Sirt1 agonist resveratrol in a concentration dependent manner. MMP-9 expression in AM cells increased significantly after siRNA interference(P < 0.05). Conclusion:Sirt1 is involved in the expression of MMP9 in AM,and may play a protective role in COPD.

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毕 辉,李玲玲,姚 欣. sirtuin-1在肺泡巨噬细胞金属基质蛋白酶9表达中作用[J].南京医科大学学报(自然科学版),2014,(8):1015-1018

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  • 收稿日期:2014-04-08
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  • 在线发布日期: 2014-08-03
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