Sirt-1和Hif-1α在慢性阻塞性肺疾病患者外周血单个核细胞中的表达及其意义

doi:10.13481/j.1671-587x.20150230

吉林大学学报(医学版) ›› 2015, Vol. 41 ›› Issue (02): 356-361.doi: 10.13481/j.1671-587x.20150230

Sirt-1和Hif-1α在慢性阻塞性肺疾病患者外周血单个核细胞中的表达及其意义

李芳¹, 关文霞², 任飞², 仝雪霞², 孙玉宁³

1. 宁夏医科大学总医院呼吸与危重医学科, 宁夏银川 750004;
2. 宁夏医科大学研究生院, 宁夏银川 750004;
3. 宁夏医科大学生物化学与分子生物学系, 宁夏银川 750004

收稿日期:2014-06-10 出版日期:2015-03-28 发布日期:2015-04-04
通讯作者: 孙玉宁, 教授, 硕士研究生导师(Tel:0951-6980113, E-mail:sunraining2008@hotmail.com) E-mail:sunraining2008@hotmail.com
作者简介:李芳(1972-), 女, 宁夏回族自治区银川市人, 副主任医师, 医学硕士, 主要从事缺氧性肺病与呼吸道感染方面的研究。
基金资助:
国家自然科学基金资助课题(81160007);宁夏回族自治区科技厅自然科学基金资助课题(NZ11204)

Expressions of Sirt-1 and Hif-1α in peripheral blood mononuclear cells of patients with chronic obstructive pulmonary disease and their significances

LI Fang¹, GUAN Wenxia², REN Fei², TONG Xuexia², SUN Yuning³

1. Department of Respiratory and Critical Care Medicine, General Hospital, Ningxia Medical University, Yinchuan 750004, China;
2. Graduate School, Ningxia Medical University, Yinchuan 750004, China;
3. Department of Biochemistry and Molecular Biology, Ningxia Medical University, Yinchuan 750004, China

Received:2014-06-10 Online:2015-03-28 Published:2015-04-04

摘要/Abstract

摘要：

目的:检测慢性阻塞性肺疾病(COPD)患者外周血单个核细胞(PBMCs)中沉默信息调节子(Sirt-1)和缺氧诱导因子1α(Hif-1α)的表达,探讨Sirt-1和Hif-1α的表达在COPD发生发展中的作用。方法:应用肺功能仪对COPD急性加重期组(n=20)、COPD稳定期组(n=22)和对照组(n=20)的研究对象进行肺功能指标测定,采用Real-time PCR和Western blotting法检测3组研究对象PBMCs中Sirt-1和Hif-1αmRNA和蛋白表达,并分析Sirt-1和Hif-1α表达水平与肺功能的关系。结果:与对照组比较,COPD急性加重期组、COPD稳定期组患者第1秒用力呼气容积占预计值百分比(FEV₁%)、第1秒用力呼气容积与用力肺活量的比值(FEV₁/FVC%)均降低(P<0.05);与COPD稳定期组比较,COPD急性加重期组患者FEV₁%和FEV₁/FVC%降低(P<0.05)。COPD急性加重期组、COPD稳定期组患者PBMCs中Sirt-1 mRNA和蛋白表达水平均低于对照组(P<0.05或P<0.01);与COPD稳定期组比较,COPD急性加重期患者PBMCs中Sirt-1 mRNA和蛋白表达水平降低(P<0.01);与对照组比较,COPD患者Hif-1α mRNA及蛋白表达水平均明显升高(P<0.05或P<0.01),COPD急性加重期患者其表达水平升高更明显(P<0.01);与COPD稳定期组比较,COPD急性加重期组患者PBMSCs中Hif-1α mRNA和蛋白表达水平升高(P<0.05)。Pearson直线相关法分析,Sirt-1 mRNA(蛋白)表达水平与患者FEV₁%(r_mRNA=0.61,r_蛋白=0.545)和FEV₁/FVC% (r_mRNA=0.513,r_蛋白=0.491)呈正相关关系,Hif-1α mRNA(蛋白)表达水平与FEV₁%(r_mRNA=-0.812,r_蛋白=-0.781)和FEV₁/FVC%(r_mRNA=-0.661,r_蛋白=-0.674)呈负相关关系(P<0.05)。结论:COPD患者PBMCs中Sirt-1基因表达水平下降,Hif-1α基因表达水平上调,二者的表达变化可能与COPD的发生发展密切相关。

关键词: 沉默信息调节子, 缺氧诱导因子1, 慢性阻塞性肺疾病, 外周血单个核细胞

Abstract:

Objective To investigate the expressions of silent information regulator 1 (Sirt-1) and hypoxia-inducible factor 1α (Hif-1α) in peripheral blood mononuclear cells (PBMCs) of the chronic obstructive pulmonary disease (COPD) patients,and to clarify their potential roles in the occurrence and development of COPD.Methods 42 patients with COPD in acute exacerbation stage (n=20) and in stable stage (n=22) and 20 healthy people were chosen.The lung function indexes of all cases were examined by lung function machine.The expressions of Sirt-1 and Hif-1α mRNA and protein in PBMCs of the objects in various groups were measured by Real-time PCR and Western blotting method. The relationships between the expression levels of Sirt-1 and Hif-1α and lung function were analyzed.Results Compared with control group,the calculated ratios of forced expiration volume in one second to predicted volume (FEV₁%) and the the calculated ratios of forced expiration volume in one second to forced vital capacity (FEV₁/FVC%) of the patients with COPD in stable stage and acute exacerbation stage were significantly decreased (P<0.05);compared with the patients in stable stage of COPD group,the FEV₁ and FEV₁/FVC% of the patients with COPD in acute exacerbation stage group were decreased (P<0.05).The expression levels of Sirt-1 mRNA and protein of the patients with COPD in acute exacerbation stage and stable stage were significantly lower than those in control group (P<0.05 or P<0.01);compared with the patients in stable stage of COPD group,the expressions of Sirt-1 mRNA and protein in PBMCs of the patients with COPD in acute exacerbation stage group were decreased(P<0.05);meanwhile,the expression levels of Hif-1α mRNA and protein of COPD patients were significantly higher than those in control group (P<0.05, P<0.01),especially in acute exacerbation stage(P<0.01);compared with the patients in stable stage of COPD group,the expressions of Hif-1α mRNA and protein in PBMSCs of the patients with COPD in acute exacerbation stage group were increased(P<0.05).The Pearson correlation analysis results showed that there were positive correlations between the expression levels of Sirt-1 mRNA (protein) and the FEV₁%(r_mRNA=0.661,r_protein=0.545) and FEV₁/FVC (r_mRNA=0.513,r_protein=0.491)(P<0.05),and there were negative correlations between the expression of Hif-1α mRNA (pretein) and FEV₁%(r_mRNA=-0.812,r_protein=-0.781) and FEV₁/FVC(r_mRNA=-0.661,r_protein=-0.674) (P<0.05).Conclusion The expression level of Sirt-1 gene is decreased and the expression level of Hif-1α gene is increased in the patients with COPD,which may be associated with the incidence and pathogenesis of COPD.

Key words: silent information regulator 1, hypoxia-inducible factor 1α, chronic obstructive pulmonary disease, peripheral blood mononuclear cells

中图分类号:

R563

李芳, 关文霞, 任飞, 仝雪霞, 孙玉宁. Sirt-1和Hif-1α在慢性阻塞性肺疾病患者外周血单个核细胞中的表达及其意义[J]. 吉林大学学报(医学版), 2015, 41(02): 356-361.

LI Fang, GUAN Wenxia, REN Fei, TONG Xuexia, SUN Yuning. Expressions of Sirt-1 and Hif-1α in peripheral blood mononuclear cells of patients with chronic obstructive pulmonary disease and their significances[J]. Journal of Jilin University Medicine Edition, 2015, 41(02): 356-361.

参考文献

[1] Barnes PJ.Cellular and molecular mechanisms of chronic obstructive pulmonary disease[J].Clin Chest Med,2014,35(1):71-86.

[2] Haigis MC,Sinclair DA.Mammalian sirtuins:biological insights and disease relevance[J].Annu Rev Pathol,2010,5(3):253-295.

[3] Rajendrasozhan S,Yang SR,Kinnula VL,et al.SIRT1,an antiinflammatory and antiaging protein,is decreased in lungs of patients with chronic obstructive pulmonary disease[J].Am J Respir Crit Care Med,2008,177(8):861-870.

[4] Hwang JW,Chung S,Sundar IK,et al.Cigarette smoke-induced autophagy is regulated by SIRT1-PARP-1-dependent mechanism:implication in pathogenesis of COPD[J].Arch Biochem Biophys,2010,500(2):203-209.

[5] Lim JH,Lee YM,Chun YS,et al.Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1alpha[J].Mol Cell,2010,38(6):864-878.

[6] Dioum EM,Chen R,Alexander MS,et al.Regulation of hypoxia-inducible factor 2alpha signaling by the stress-responsive deacetylase sirtuin 1[J].Science,2009,324(5932):1289-1293.

[7] 中华医学会呼吸病学分会慢性阻塞性肺疾病学组.慢性阻塞性肺疾病诊治指南(2007年修订版)[J].中华结核和呼吸杂志,2007,30(1):8-17.

[8] 张振芳,王在义.COPD基因研究进展[J].临床肺科杂志,2014,19(1):124-127.

[9] Moynihan KA,Grimm AA,Plueger MM,et al.Increased dosage of mammalian Sir2 in panereatic beta cells enhances glucose-stimulated insulin secretion in mice[J].Cell Metab,2005,2(2):105-117.

[10] Ota H,Eto M,Ogawa S,et al.Sirt1/eNOS axis as a potential target against vascular senescence,dysfunction and atherosclerosis[J].J Atheroscler Thromb,2010,17 (5):431-435.

[11] Li X,Zhang S,Blander G,et al.SIRT1 deacetylates and positively regulates the nuclear receptor LXR[J].Mol Cell,2007,28(1):91-106.

[12] Nakamaru Y,Vuppusetty C,Wada H,et al.A protein deacetylase SIRT1 is a negative regulator of metalloproteinase-9[J].FASEB J,2009,23(9):2810-2819.

[13] Fong GH.Mechanisms of adaptive angiogenesis to tissue hypoxia[J].Angiogenesis,2008,11(2):121-140.

[14] Adams JM,Difazio LT,Rolandelli RH,et al.HIF-1:a key mediator in hypoxia[J].Acta Physiol Hung,2009,96 (1):19-28.

[15] Schumacker PT.Hypoxia-inducible factor-1 (HIF-1) [J].Crit Care Med,2005,33(12 Suppl):S423-S425.

[16] 魏文婷,李冰,贾晔然,等.慢性阻塞性肺疾病患者肺组织中缺氧诱导因子1α的表达变化[J].中国病理生理杂志,2013,29(9):1700-1703.

[17] 徐永芳,孙维罗,孙燕.ET-1、VEGF、HIF-1α在COPD合并肺动脉高压形成中的意义[J].心脑血管病防治,2010,10(5):339-340.

[18] Mizuno S,Bogaard HJ,Gomez-Arroyo J,et al.MicroRNA-199a-5p is associated with hypoxia-inducible factor-1α expression in lungs from patients with COPD[J].Chest,2012,142(3):663-672.

[19] Putra AC,Tanimoto K,Arifin M,et al.Genetic variations in detoxification enzymes and HIF-1α in Japanese patients with COPD[J].Clin Respir J,2013,7(1):7-15.

[20] 王宗强,于荣秀,吴健红,等.缺氧诱导因子-1 在COPD患者外周血单个核细胞中的表达[J].广东医学,2011,32(1):64-66.

Sirt-1和Hif-1α在慢性阻塞性肺疾病患者外周血单个核细胞中的表达及其意义

Expressions of Sirt-1 and Hif-1α in peripheral blood mononuclear cells of patients with chronic obstructive pulmonary disease and their significances

RichHTML

PDF (PC)

赞

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

Metrics

本文评价

推荐阅读 0

[1]	侯海龙, 唐颖, 曲兴龙, 华树成. 右美托咪定联合无创通气治疗AECOPD并发肺性脑病患者的临床疗效及安全性评价[J]. 吉林大学学报(医学版), 2018, 44(05): 1014-1019.
[2]	王淼, 母润红, 李明成, 李洪杰. RNAi沉默survivin和HIF-1α基因对胃癌BGC-823细胞体外增殖和凋亡的影响[J]. 吉林大学学报(医学版), 2018, 44(04): 753-758.
[3]	蓝永洪, 饶朗毓, 杨智, 黄明媚, 牛海艳, 齐亚灵. 妊娠高血压综合征患者胎盘组织中HIF-1α和HSP70的表达及其意义[J]. 吉林大学学报(医学版), 2018, 44(02): 346-349.
[4]	张雪阳, 马骥, 孟广平, 王琦, 李伟, 徐艳玲, 张捷, 高鹏. 基于吉林省长春市区居民肺功能筛查的慢性阻塞性肺疾病患病现况调查分析[J]. 吉林大学学报(医学版), 2017, 43(05): 1047-1052.
[5]	亓慧琴, 张连莲, 邢利平, 孙璐瑶, 刘颖, 于振香. 慢性阻塞性肺疾病患者应用异丙托溴铵联合乙酰半胱氨酸治疗前后血清中TGF-β和MMP-9水平的变化及其临床意义[J]. 吉林大学学报(医学版), 2016, 42(04): 777-782.
[6]	李娜, 何叶, 李敏超. 机械压力敏感性通道蛋白表达水平与COPD患者气道重塑的关联性分析[J]. 吉林大学学报(医学版), 2016, 42(02): 277-282.
[7]	王国强, 牟佳, 李元, 袁语泽, 王昱博, 宋晨雪, 谢婧书, 郑敬彤, 王放. NLRP3、AIM2和CASP1基因在慢性阻塞性肺疾病急性加重发病中的作用[J]. 吉林大学学报(医学版), 2016, 42(01): 130-133.
[8]	唐文芳, 刘日辉, 于雅琴, 刘晶, 高鹏, 王珂. 2000—2014年中国40岁以上成人慢性阻塞性肺疾病患病率的Meta分析[J]. 吉林大学学报(医学版), 2015, 41(05): 961-968.
[9]	吴忠练, 黄学宽, 骆言, 张超男, 蒋娟. 贝母瓜蒌散对慢性阻塞性肺疾病大鼠肺组织中血管紧张素Ⅱ表达水平的影响[J]. 吉林大学学报(医学版), 2015, 41(03): 527-531.
[10]	陈新, 刘特, 王树越, 张文静, 谢静芳, 秦元明, 钱东华, 叶琳. 日平均气温对医院慢性阻塞性肺疾病急性加重患者住院人次的影响[J]. 吉林大学学报(医学版), 2015, 41(02): 389-392.
[11]	张文静, 井宏宇, 许弘邦, 钱东华. IL-4-33C/T和IL-6-572C/G基因多态性与慢性阻塞性肺疾病易感性的关联性分析[J]. 吉林大学学报(医学版), 2015, 41(01): 145-149.
[12]	徐晓光，姜振宇，杜敏娟，杨亚琴，蒋颖超. 沙美特罗/丙酸氟替卡松联合N-乙酰半胱氨酸治疗慢性阻塞性肺疾病的疗效评价[J]. 吉林大学学报(医学版), 2014, 40(04): 870-874.
[13]	郭晓雪，马丽伟，李晓宁，刘颖，孙璐瑶，张连莲，于振香. 乙酰半胱氨酸联合异丙托溴铵对控制大鼠慢性阻塞性肺疾病病程进展的作用[J]. 吉林大学学报(医学版), 2013, 39(4): 694-698.
[14]	方盼盼，宫璀璀，仓宝成，李正民，李宗杰，李文莉，朱传杰，王迎涛. HIF-1α和RelA基因在急进高原正常人外周血单个核细胞中的表达及其与急性高原反应的关联性[J]. 吉林大学学报(医学版), 2013, 39(4): 781-785.
[15]	顾延会，欧阳瑶，孙得胜. CCL20抗体对慢性阻塞性肺疾病大鼠外周血和肺泡灌洗液中树突状细胞表面因子表达的影响[J]. 吉林大学学报(医学版), 2013, 39(2): 236-240.