[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