厄多司坦对急性肺损伤小鼠肺内Nrf2表达的影响

doi:10.3969/j.issn.1671-7171.2017.09.003

摘要
图/表
参考文献
相关文章 (15)

全文: PDF (0 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要【目的】探讨厄多司坦对脂多糖(LPS)诱导的小鼠急性肺损伤(ALI)小鼠肺内抗氧化转录因子Nrf2表达的影响。【方法】健康雄性C57bl/6小鼠24只随机分为对照组、ALI组和厄多司坦组,每组8只。采用气管注射LPS(5 mg/kg)复制小鼠ALI动物模型。厄多司坦组通过提前30 min灌胃(150 mg/kg)给予预处理,造模12 h后处理小鼠。HE染色观察小鼠肺组织形态学改变;检测丙二醛(MDA)含量和超氧歧化物(SOD)活性反映肺组织氧化应激;Western blot法检测肺组织核内Nrf2的表达;Real-time PCR检测肺组织HO-1和SOD mRNA含量。【结果】厄多司坦可改善LPS诱导的ALI小鼠肺组织病理形态学改变,降低肺组织内MDA含量,而增加SOD活性。厄多司坦亦可显著性增加ALI小鼠肺组织细胞核内Nrf2的表达,并显著增加Nrf2下游靶基因HO-1和SOD mRNA的表达。【结论】厄多司坦能减轻LPS诱导的小鼠ALI,通过增强ALI小鼠肺内抗氧化转录因子Nrf2的核转位及转录活性可能是其机制所在。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	董良
	周祎琦
	毛振宇
	陈永琴

关键词 ：肺/损伤, 硫乙醇酸盐类/药理学, 噻吩类/药理学, 急性病, 脂多糖类, 肺疾病/化学诱导, 氧化性应激

Abstract：【Objective】To investigate the effect of erdosteine on the expression of antioxidant transcription factor Nrf2 in lung of acute lung injury (ALI) mice induced by lipopolysaccharide (LPS).【Methods】The healthy male C57bl/6 mice were randomly divided into control group, ALI group and erdosteine group (n=8). The mouse model of ALI was reproduced by intratracheal injection of LPS (5 mg/kg). Erdosteine (150 mg/kg) was given 30 min before delivery and the mice were sacrificed 12 h later. HE staining was used to observe the morphological changes of lung tissue in mice. The content of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured to reflect the oxidative stress in lung tissue. The expression of Nrf2 in lung tissue was detected by Western blot. Real-time PCR was used to detect the contents of HO-1 and SOD mRNA in lung tissue.【Results】Erdosteine could improve the histopathological changes of lung tissue induced by LPS in ALI mice, decrease the content of MDA in lung tissue and increase the activity of SOD. Erdosteine could also significantly increase the expression of Nrf2 in the nucleus of ALI mice and significantly increase the expression of HO-1 and SOD mRNA.【Conclusion】Erdosteine can alleviate LPS-induced ALI in mice.The mechanism may be due to the enhancement of the nuclear translocation and transcription activity of the antioxidant transcription factor Nrf2 in the lung of ALI mice.

Key words： Lung/IN Thioglycolates/PD Thiophenes/PD Acute Disease Lipopolysaccharides Lung Diseases/CI Oxidative Stress

收稿日期: 2017-08-14

PACS:

R563

基金资助:遵义医学院附属医院博士启动基金(编号:201703);遵义医学院大学生创新创业训练计划项目(编号:20162312)

引用本文:

董良,周祎琦,毛振宇,陈永琴. 厄多司坦对急性肺损伤小鼠肺内Nrf2表达的影响[J]. 医学临床研究, 2017, 34(9): 1673-1676.
DONG Liang, ZHOU Yi-qi,MAO Zhen-yu,et al. Effect of Erdosteine on the Expression of Nrf2 in Mice Acute Lung Injury. JOURNAL OF CLINICAL RESEARCH, 2017, 34(9): 1673-1676.

链接本文:

http://www.jcr.net.cn/CN/10.3969/j.issn.1671-7171.2017.09.003 或 http://www.jcr.net.cn/CN/Y2017/V34/I9/1673

[1]Ranieri VM,Rubenfeld GD,Thompson BT,et al.Acute respiratory distress syndrome: the Berlin Definition[J].JAMA,2012,307(23): 2526-2533.
[2]Bellani G,Laffey JG,Pham T,et al.Epidemiology,Patterns of Care,and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries [J].JAMA,2016,315(8): 788-800.
[3]Ugurel V,Cicek AC,Cemek M,et al.Antioxidant and antiapoptotic effects of erdosteine in a rat model of ovarian ischemia-reperfusion injury [J].Iran J Basic Med Sci,2017,20(1): 53-58.
[4]Erdem A,Gedikli E,Yersal N,et al.Protective role of erdosteine pretreatment on oleic acid-induced acute lung injury [J].J Surg Res,2017,213: 234-242.
[5]Hayashi K,Hosoe H,Kaise T,et al.Protective effect of erdosteine against hypochlorous acid-induced acute lung injury and lipopolysaccharide-induced neutrophilic lung inflammation in mice [J].J Pharm Pharmacol,2000,52(11): 1411-1416.
[6]Demiralay R,Gursan N,Ozbilim G,et al.Comparison of the effects of erdosteine and N-acetylcysteine on apoptosis regulation in endotoxin-induced acute lung injury [J].J Appl Toxicol,2006,26(4): 301-308.
[7]Alkan A,Eroglu F,Eroglu E,et al.Protective effects of N-acetylcysteine and erdosteine on hemorrhagic shock-induced acute lung injury [J].Eur J Emerg Med,2006,13(5): 281-285.
[8]Marchev AS,Dimitrova PA,Burns AJ,et al.Oxidative stress and chronic inflammation in osteoarthritis: can NRF2 counteract these partners in crime [J]?Ann N Y Acad Sci,2017.
[9]Cheng X,He S,Yuan J,et al.Lipoxin A4 attenuates LPS-induced mouse acute lung injury via Nrf2-mediated E-cadherin expression in airway epithelial cells [J].Free Radic Biol Med,2016,93: 52-66.
[10]Shan Y,Akram A,Amatullah H,et al.ATF3 protects pulmonary resident cells from acute and ventilator-induced lung injury by preventing Nrf2 degradation [J].Antioxid Redox Signal,2015,22(8): 651-668.
[11]Kim SJ,Park C,Lee JN,et al.Erdosteine protects HEI-OC1 auditory cells from cisplatin toxicity through suppression of inflammatory cytokines and induction of Nrf2 target proteins [J].Toxicol Appl Pharmacol,2015,288(2): 192-202.
[12]Elkady AA,Ibrahim IM.Protective effects of erdosteine against nephrotoxicity caused by gamma radiation in male albino rats [J].Hum Exp Toxicol,2016,35(1): 21-28.
[13]Xu D,Chen L,Chen X,et al.The triterpenoid CDDO-imidazolide ameliorates mouse liver ischemia-reperfusion injury through activating the Nrf2/HO-1 pathway enhanced autophagy [J].Cell Death Dis,2017,8(8): e2983.
[14]Yadav A,Sunkaria A,Singhal N,et al.Resveratrol loaded solid lipid nanoparticles attenuate mitochondrial oxidative stress in vascular dementia by activating Nrf2/HO1 pathway [J].Neurochem Int,2017.
[15]Guzel A,Kayhan S,Tutuncu S,et al.Attenuation of bleomycin induced lung fibrosis by erdosteine and inhibition of the inducible nitric oxide synthase [J].Bratisl Lek Listy,2015,116(3): 196-202.
[16]Park JS,Park MY,Cho YJ,et al.Anti-inflammatory Effect of Erdosteine in Lipopolysaccharide-Stimulated RAW 264.7 Cells [J].Inflammation,2016,39(4): 1573-1581.
[17]Hyung JH,Ahn CB,Il Kim B,et al.Involvement of Nrf2-mediated heme oxygenase-1 expression in anti-inflammatory action of chitosan oligosaccharides through MAPK activation in murine macrophages [J].Eur J Pharmacol,2016,793: 43-48.