|本期目录/Table of Contents|

[1]侯美伊,桑楠.二氧化氮(NO2)吸入暴露对大鼠心肌线粒体的损伤作用[J].应用与环境生物学报,2014,20(06):1033-1038.[doi:10.3724/SP.J.1145.2014.05019]
 HOU Meiyi,SANG Nan.The damage of NO2 inhalation exposure to myocardial cell mitochondria in rats[J].Chinese Journal of Applied & Environmental Biology,2014,20(06):1033-1038.[doi:10.3724/SP.J.1145.2014.05019]
点击复制

二氧化氮(NO2)吸入暴露对大鼠心肌线粒体的损伤作用()
分享到:

《应用与环境生物学报》[ISSN:1006-687X/CN:51-1482/Q]

卷:
20卷
期数:
2014年06期
页码:
1033-1038
栏目:
研究论文
出版日期:
2014-12-31

文章信息/Info

Title:
The damage of NO2 inhalation exposure to myocardial cell mitochondria in rats
作者:
侯美伊 桑楠
山西大学环境与资源学院 太原 030006
Author(s):
HOU Meiyi SANG Nan
College of Environmental and Resource Sciences, Shanxi University, Taiyuan 030006, China
关键词:
NO2心肌线粒体PGC-1αNRF1TFAM心血管系统疾病
Keywords:
NO2 myocardial mitochondria PGC-1α NRF1 TFAM CVD
分类号:
X174
DOI:
10.3724/SP.J.1145.2014.05019
文献标志码:
A
摘要:
除呼吸系统外心脏可能是二氧化氮(NO2)作用的重要靶器官之一,而线粒体是心脏运作高度依赖的细胞器,故通过研究线粒体相关指标的变化,探究空气NO2污染与心血管系统疾病的相关性对有效预防这类污染物暴露和干预由此引发的疾病治疗具有重要意义.建立Wistar大鼠NO2动式吸入染毒模型,考察慢性(对照、1 × 10-6和2.5 × 10-6)和急性(对照、2.5 × 10-6、5 × 10-6和10 × 10-6)暴露条件下大鼠心肌细胞线粒体超微结构变化、线粒体膜电位和活性功能水平变化,以及调控线粒体呼吸链组分相关因子PGC-1α、NRF1和TFAM蛋白表达变化.结果显示,长期低浓度NO2暴露致使心肌细胞线粒体数量减少并伴有肿胀;活性均显著降低,分别为对照组的0.79倍(P < 0.05)和0.56倍(P < 0.05);膜电位较对照组均显著下降,分别为0.89倍(P < 0.05)和0.79倍(P < 0.05);调控线粒体呼吸链组分相关因子PGC-1α、NRF1和TFAM蛋白表达较对照组下调,并在2.5×10-6时均显现出显著性差距,分别为对照组的0.76倍(P < 0.05)、0.85倍(P < 0.001)和0.52倍(P < 0.05).而急性较高浓度NO2暴露时结果不同,大鼠心肌细胞线粒体数量增加;活性在5 × 10-6和10 × 10-6时显著性上升,分别为对照组的1.52倍(P < 0.001)和2.12倍(P < 0.001);膜电位在各浓度均显著增加,分别为对照组的1.50倍(P < 0.05)、1.62倍(P < 0.05)和2.25倍(P < 0.001);调控线粒体呼吸链组分相关因子PGC-1α、NRF1和TFAM表达依赖性上调,同时在10 × 10-6下呈现显著增高趋势,分别为对照组的1.51倍(P < 0.001)、1.47倍(P < 0.05)和1.60倍(P < 0.001).本研究表明,长期低浓度NO2暴露会引起心肌细胞线粒体氧化磷酸化功能减弱,进而导致线粒体功能退化;然而,急性较高浓度NO2暴露则引发相反的生物学效应,大鼠心肌细胞线粒体增强相关功能以适应外界刺激,这与线粒体功能代偿作用有关.由于线粒体功能和结构的完整性对于心血管系统疾病的生理机能至关重要,其损伤很可能是空气NO2污染与心血管系统疾病发生发展相关的重要分子机制.
Abstract:
The heart is suggested to be one of the important target organs of nitrogen dioxide (NO2) besides the respiratory system. Since effective operation of the heart is based on mitochondria, it is of great significance to study the correlation between NO2 pollution and mitochondrial structure and function for prevention and intervention of cardiovascular diseases (CVD) after NO2 exposure. In the present study, we established NO2 inhalation exposure model using Wistar rats with chronic (control, 1 × 10-6, 2.5 × 10-6) and acute (control, 2.5 × 10-6, 5 × 10-6, 10 × 10-6) exposure, to investigate the mitochondrial ultrastructure of myocardial cell. The mitochondrial function was detected by membrane potential and activity. The protein levels of mitochondrial respiratory chain transcription factors PGC-1α, NRF1, and TFAM were assayed by Western blot. The results showed a decrease of the number of mitochondria and swelling of myocardial cells after chronic and low concentration NO2 exposure. The mitochondria activity declined significantly, being 0.79 times (P < 0.05) and 0.56 times (P < 0.05) respectively of the control. The membrane potential was significantly lower, being 0.89 times (P < 0.05) and 0.79 times (P < 0.05) respectively of the control. Expressions of PGC-1α, NRF1 and TFAM declined significantly to 76% (P < 0.05), 85% (P < 0.001) and 52% (P < 0.05) respectively in myocardial cell after 2.5 × 10-6 chronic and low concentration NO2 exposure. However, after acute and high concentration NO2 stimulation the number of myocardial cell mitochondria increased. The mitochondria activity increased to 1.52 (P < 0.001) and 2.12 (P < 0.001) times respectively with 5 × 10-6 and 10 × 10-6 NO2. The membrane potential increased significantly to 1.50 (P < 0.05), 1.62 (P < 0.05) and 2.25 (P < 0.001) times respectively with 2.5 × 10-6, 5 × 10-6 and 10 × 10-6 NO2. The expression levels of PGC-1α, NRF1 and TFAM all increased significantly in myocardial cell of rats, to 1.51 (P < 0.001), 1.47 (P < 0.05) and 1.60 (P < 0.001) times respectively under 10×10-6 exposure. The results indicated that chronic and low concentration NO2 exposure causes mitochondrial dysfunction by myocardial mitochondria oxidative phosphorylation weakening. Meanwhile, the opposite biological effect after acute and high concentration NO2 stimulation could be due to the compensative effect. The mitochondrial structure and function damage might be one of the molecular mechanisms of CVD induced by NO2 pollution.

参考文献/References:

1 Hesterberg TW, Bunn WB, McClellan RO, Hamade AK, Long CM, Valberg PA. Critical review of the human data on short-term nitrogen dioxide (NO2) exposures: evidence for NO2 no-effect levels [J]. Crit Rev Toxicol, 2009, 39 (9): 743-781
2 Pathmanathan S, Krishna MT, Blomberg A, Helleday R, Kelly FJ, Sandstr?m T, Frew AJ. Repeated daily exposure to 2 ppm nitrogen dioxide upregulates the expression of IL-5, IL-10, IL-13, and ICAM-1 in the bronchial epithelium of healthy human airways [J]. Occup Environ Med, 2003, 60 (11): 892-896
3 Hussain I, Jain VV, O’Shaughnessy P, Businga TR, Kline J. Effect of nitrogen dioxide exposure on allergic asthma in a murine model [J]. Chest, 2004, 126 (1): 198-204
4 陈良恩, 王永新, 魏日胞, 詹皓, 辛益妹. 复方红景天制剂对高+Gz 应激大鼠心肌线粒体超微结构的影响[J]. 中华老年多器官疾病杂志, 2011, 10 (3): 261-264 [Chen L’E, Wang YX, Wei RB, Zhang H, Xin YM. Effect of rhodiola crenulata compounds on ultrastructure injury of myocardial mitochondria in rats exposured to high +Gz stress [J]. Chin J Mult Organ Dis Elderly, 2011, 10 (3): 261-264]
5 陈永红, 杜冠华. 线粒体与衰老[J]. 中国药理学通报, 2000, 16 (5): 485-488 [Chen YH, Du GH. Mitochondria and aging [J]. Chin Pharmacol Bull, 2000, 16 (5): 485-488]
6 Dominic EA, Ramezani A, Anker SD, Verma M, Mehta N, Rao, M. Mitochondrial cytopathies and cardiovascular disease [J]. Heart, 2014, 100 (8): 611-618
7 Kumie A, Emmelin A, Wahlberg S, Berhane Y, Ali A, Mekonen E, Brandstrom D. Sources of variation for indoor nitrogen dioxide in rural residences of Ethiopia [J]. Environ Health, 2009, 8 (1): 51-62
8 Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding [J]. Anal Biochem, 1976, 72 (1): 248-254
9 Szyszkowicz M. Ambient air pollution and daily emergency department visits for ischemic stroke in Edmonton, Canada [J]. Int J Occup Med Environ Health, 2008, 21 (4): 295-300
10 Guo Y, Tong S, Li S, Barnett AG, Yu W, Zhang Y, Pan, X. Gaseous air pollution and emergency hospital visits for hypertension in Beijing, China: a time-stratified case-crossover study [J]. Environ Health, 2010, 9 (1): 57
11 孙建平, 谭竹钧, 韩雅莉. 细胞凋亡检测方法的研究进展[J]. 生物技术通报, 2012 (1): 54-59 [Sun JP, Tan ZY, Han YL. Research and development of the methods to detection apoptosis [J]. Biotechnol Bul, 2012, (1): 54-59]
12 陈慧莉, 李建华, 王树庆. 线粒体跨膜电位和细胞凋亡相关性的研究[J]. 医学综述, 2007, 13 (14): 1041-1043 [Chen HL, Li JH, Wang SQ. Correlative study between mitochondrial transmembrane potential and apoptosis [J]. Med Recap, 2007, 13 (14): 1041-1043]
13 Parisi MA, Clayton DA. Similarity of human mitochondrial transcription factor 1 to high mobility group proteins [J]. Science, 1991, 252 (5008): 965-969
14 Scarpulla RC. Transcriptional paradigms in mammalian mitochondrial biogenesis and function [J]. Physiol Rev, 2008, 88 (2): 611-638
15 Garnier A, Fortin D, Deloménie C, Momken I, Veksler V, Ventura-Clapier R. Depressed mitochondrial transcription factors and oxidative capacity in rat failing cardiac and skeletal muscles [J]. J Physiol, 2003, 551 (2): 491-501
16 Ryan MT, Hoogenraad NJ. Mitochondrial-nuclear communications. Annu Rev Biochem, 2007, 76: 701-722
17 Pilegaard H, Saltin B, Neufer P D. Exercise induces transient transcriptional activation of the PGC-1α gene in human skeletal muscle [J]. J Physiol, 2003, 546 (3): 851-858
18 Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM. A cold- inducible coactivator of nuclear receptors linked to adaptive thermogenesis [J]. Cell, 1998, 92 (6): 829-839

相似文献/References:

[1]韩明,李广科,桑楠.慢性吸入二氧化氮诱发大鼠DNA-蛋白质交联和微核效应[J].应用与环境生物学报,2013,19(06):941.[doi:10.3724/SP.J.1145.2013.00941]
 HAN Ming,LI Guangke,SANG Nan.DNA-protein Crosslinks and Micronuclei Induced by Chronic Nitrogen Dioxide Inhalation in Rats[J].Chinese Journal of Applied & Environmental Biology,2013,19(06):941.[doi:10.3724/SP.J.1145.2013.00941]

备注/Memo

备注/Memo:
教育部高等学校博士学科点专项科研基金项目(20121401110003,20131401110005)资助 Supported by the Specialized Research Fund for the Doctoral Program of Higher Education of China (SRFDP, 20121401110003, 20131401110005)
更新日期/Last Update: 2015-01-05