[1]李明,孙守兵,周越,等.去甲肾上腺素诱导人巨噬细胞MMP-9的表达及机制[J].第三军医大学学报,2012,34(17):1758-1761.
　Li Ming,Sun Shoubing,Zhou Yue,et al.Norepinephrine induces expression of matrix metalloproteinase-9 in human macrophages and its mechanisms[J].J Third Mil Med Univ,2012,34(17):1758-1761.
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
34卷
期数:
2012年第17期
页码:
1758-1761
栏目:
论著
出版日期:
2012-09-15

文章信息/Info

Title:
Norepinephrine induces expression of matrix metalloproteinase-9 in human macrophages and its mechanisms
作者:
李明; 孙守兵; 周越; 庞晓明; 席娟; 金泰宇; 姚文平
连云港市中医院：药学部，针灸科；西安交通大学药理学系；济宁医学院附属医院手术室；连云港市第二人民医院药学部
Author(s):
Li Ming;  Sun Shoubing;  Zhou Yue;  Pang Xiaoming;  Xi Juan;  Jin Taiyu;  Yao Wenping
Department of Pharmacy, Department of Acupuncture and Moxibustion, Lianyungang Hospital of Traditional Chinese Medicine, Lianyungang, Jiangsu Province, 222000; Faculty of Pharmacology, Xi’an Jiaotong University School of Medicine, Xi’an, Shaanxi Province, 710061; Department of Operating Room, Affiliated Hospital of Jining Medical College, Jining, Shandong Province, 272029;Department of Pharmacy, Second People’s Hospital of Lianyungang, Lianyungang, Jiangsu Province, 222000, China
关键词:
去甲肾上腺素; 巨噬细胞; 基质金属蛋白酶-9; 动脉粥样硬化
Keywords:
norepinephrine;  macrophages;  matrix metalloproteinase-9;  atherosclerosis
分类号:
R963.21;R394.2;R543.5
文献标志码:
A
摘要:
目的      观察去甲肾上腺素（norepinephrine，NE）预处理人巨噬细胞基质金属蛋白酶-9（MMP-9）的表达及其致动脉粥样硬化机制。      方法       体外培养的U937巨噬细胞，以10-10、10-9、10-8、10-7 mol/L NE分别刺激细胞0、1、3、6、12、24 h。RT-PCR法测细胞MMP-9 mRNA水平，Western blot法检测细胞MMP-9蛋白表达，ELISA法测细胞培养液上清中MMP-9蛋白水平的表达。预先加入抗氧化剂NAC(10 mmol/L）和NAD(P)H氧化酶抑制剂DPI(10-5 mol/L)孵育1 h后再用不同浓度的NE分别刺激细胞24 h，用荧光探针法检测细胞内ROS的生成；用RT-PCR及ELISA法检测细胞MMP-9 mRNA和蛋白的表达。      结果       NE浓度时间依赖性地增加巨噬细胞MMP-9 mRNA（10-7 mol/L NE为对照组的4.65倍，P<0.01）及蛋白（10-7 mol/L NE为对照组的4.14倍，P<0.01）表达；随着NE浓度的升高，ROS的生成分别为对照组的2.18、3.22、3.64、4.50倍（P<0.01）。NAC和DPI都一定程度地抑制了MMP-9 mRNA[DPI组为NE组的0.752倍（P<0.05），NAC组为NE组的0.500倍（P<0.01）]和蛋白（DPI组为NE组的0.698倍，NAC组为NE组的0.671倍，均P<0.05）的表达。      结论       NE浓度和时间依赖性地诱导人巨噬细胞U937 MMP-9的表达，通过NAD(P)H氧化酶介导的ROS通路而促进炎症反应，促进AS的发生、发展。
Abstract:
Objective      To investigate the effect of norepinephrine (NE) on the expression of matrix metalloproteinase-9 (MMP-9) in human macrophages, and to explore its pro-inflammatory and pro-atherosclerotic mechanisms.       Methods      Murine U937 macrophages were cultured and pretreated with antioxidant NAC (10 mmol/L) and NAD(P)H oxidase inhibitor DPI (10-5 mol/L) for 1 h. Then the cells were treated with different concentrations (10-10, 10-9, 10-8 and 10-7 mol/L) of NE at different time points (0, 1, 3, 6, 12 and 24 h). MMP-9 mRNA level was analyzed by RT-PCR. MMP-9 protein expression was measured by Western blotting. MMP-9 protein level in cell supernatant was detected by ELISA. Intracellular reactive oxygen species (ROS) generation was observed with fluorescence probes, and intracellular MMP-9 mRNA and protein expressions were detected by RT-PCR and ELISA.       Results      The mRNA expression level (4.65 times that of the control group in the 10-7 mol/L NE group, P<0.01) and protein expression level (4.14 times that of the control group in the 10-7 mol/L NE group, P<0.01) of MMP-9 in macrophages were increased by NE in a dose- and time-dependent manner. The levels of ROS were 2.18, 3.22, 3.64 and 4.50 times that of the control group in the 10-10, 10-9, 10-8 and 10-7 mol/L NE groups, respectively (P<0.01). NAC and DPI significantly antagonized the effect of NE on MMP-9 mRNA (DPI group was 75.2% that of the control group, P<0.05; NAC group was 50% that of the control group, P<0.01) and protein expressions (DPI group was 69.8% that of the control group, P<0.05; NAC group was 67.1% that of the control group, P<0.05).       Conclusion      NE upregulates MMP-9 expression in U937 cells in a dose- and time-dependent manner, and induces ROS secretion via NAD(P)H oxidase, which mediates the pro-inflammatory effect of NE to promote the formation and development of atherosclerosis.

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更新日期/Last Update: 2012-08-31