您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报(医学版) ›› 2014, Vol. 52 ›› Issue (8): 47-51.doi: 10.6040/j.issn.1671-7554.0.2014.052

• 临床医学 • 上一篇    下一篇

瓣膜病患者钙调神经磷酸酶-活化T细胞核因子通路与心房纤颤的关系

李丛1, 王建春1, 赵勇1, 邹承伟2, 孙慧3, 张庆1   

  1. 1. 山东大学附属省立医院保健心血管科, 山东 济南 250021;
    2. 山东大学附属省立医院心脏外科, 山东 济南 250021;
    3. 山东大学附属济南市中心医院心内科, 山东 济南 250013
  • 收稿日期:2014-01-23 修回日期:2014-04-11 出版日期:2014-08-10 发布日期:2014-08-10
  • 通讯作者: 王建春。E-mail:wangjianchun@medmail.com.cn E-mail:wangjianchun@medmail.com.cn
  • 基金资助:
    山东省科技发展计划(2013G0021819);山东省自然科学基金(ZR2011HM072,ZR2010HQ048);山东省医药卫生科技发展计划(2011BJZD05);国家自然科学青年基金(30900608);济南市青年科技明星计划(20080112)

Association between calcineurin-nuclear factor of activated T cell pathway and atrial fibrillation in patients with valvular heart disease

LI Cong1, WANG Jianchun1, ZHAO Yong1, ZOU Chengwei2, SUN Hui3, ZHANG Qing1   

  1. 1. Department of Geriatric Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China;
    2. Department of Cardiac Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China;
    3. Department of Cardiology, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, Shandong, China
  • Received:2014-01-23 Revised:2014-04-11 Online:2014-08-10 Published:2014-08-10

摘要: 目的 探讨瓣膜病患者钙调神经磷酸酶-活化T细胞核因子通路(CaN-NFAT通路)与心房纤颤的关系。方法 选择因瓣膜病接受换瓣手术治疗患者43例,根据心律状况分为慢性持续性房颤组(n=24)和窦性心律组(n=19),术前抽取外周静脉血,术中取右心耳心肌组织。在查体中心抽取20例健康查体者的静脉血标本为健康对照组。以β-actin为内参照,采用 RT-PCR法分别检测房颤组和窦性心律组外周血淋巴细胞及心肌组织中的CaN催化亚基(CnA)的α(CnAα)、β(CnAβ)异构体、NFATc3、NFATc4的mRNA水平,健康对照组外周血淋巴细胞中的CnAα、CnAβ、NFATc3和NFATc4的mRNA水平。结果 与窦性心律组和健康对照组相比,房颤组外周血淋巴细胞中CnAα、CnAβ、NFATc3的mRNA水平升高(P<0.05)。与窦性心律组相比,房颤组心肌细胞中的CnAα、CnAβ、NFATc3和NFATc4的mRNA水平升高(P<0.05)。结论 钙调神经磷酸酶-活化T细胞核因子通路可能与瓣膜病患者心房纤颤有关。

关键词: 瓣膜病, 钙调神经磷酸酶, 活化T细胞核因子, 房颤, mRNA

Abstract: Objective To explore the association between calcineurin-nuclear factor of activated T cell pathway (CaN-NFAT pathway) and atrial fibrillation (AF) in patients with valvular heart disease (VHD). Methods A total of 43 patients with VHD who underwent valve replacement surgery were enrolled, including 24 with chronic persistent AF and 19 with sinus rhythm (SR). Peripheral venous blood samples were taken before surgery and cardiac muscle tissues were taken from the right atrial appendages during surgery. Blood samples were also collected from 20 healthy controls. Transcription of α- and β- isoforms of CaN subunit A (CnA) and NFATc3, NFATc4 in peripheral lymphocytes and right atrial appendages were assessed by real-time reverse transcription polymerase chain reaction (RT-PCR), with β-actin as an internal reference. Results Compared with SR patients and healthy controls, the mRNA levels ofCnA α-isoform, CnA β-isoform and NFATc3 were elevated in peripheral lymphocytes from AF patients (P<0.05). Compared with SR patients, the mRNA levels of CnA α-isoform, CnA β-isoform, NFATc3 and NFATc4 were elevated in cardiac tissues from AF patients (P<0.05). Conclusion CaN-NFAT pathway is associated with AF in patients with VHD.

Key words: Atrial fibrillation, Valvular heart disease, Calcineurin, Nuclear factor of activated T cell, mRNA

中图分类号: 

  • R541.7
[1] Zhou Z, Hu D. An epidemiological study on the prevalence of atrial fibrillation in the Chinese population of mainland China[J]. J Epidemiology, 2008, 18(5):209-216.
[2] 周自强, 胡大一, 陈捷, 等. 中国心房颤动现状的流行病学研究.中华内科杂志, 2004, 43(7):491-494.
[3] Li H, Rao A, Hoqan P G. Interaction of calcineurin with substrates and targeting proteins[J]. Trends Cell Biol, 2011, 21(2):91-103.
[4] Musson R E, Cobbaert C M, Smit N P. Molecular diagnostics of calcineurin-related pathologies[J]. Clin Chem, 2012, 58(3):511-522.
[5] Wilkins B J, De Windt L J, Bueno O F, et al. Targeted disruption of NFATc3, but not NFATc4, reveals an intrinsic defect in calcineurin-mediated cardiac hypertrophic growth[J]. Mol Cell Biol, 2002, 22(21):7603-7613.
[6] Ritter O, Hack S, Schuh K, et al. Calcineurin in human heart hypertrophy[J]. Circulation, 2002, 105(19):2265-2269.
[7] Lim H W, De Windt L J, Mante J, et al. Reversal of cardiac hypertrophy in transgenic disease models by calcineurin inhibition[J]. J Mol Cell Cardiol, 2000, 32(4):697-709.
[8] Colella M, Grisan F, Robert V, et al. Ca2+ oscillation frequency decoding in cardiac hypertrophy: role of calcineurin/NFAT as Ca2+ signal integrators[J]. Proc Nati Acad Sci USA, 2008, 105(8):2859-2864.
[9] 王建春, 王传霞, 楼红, 等. 心衰患者心脏超声改变与心肌钙调神经磷酸酶的关系[J]. 医学影像学杂志, 2005, 15(3):192-194.
[10] 王萌萌, 赵勇, 刘伟, 等. 心力衰竭患者外周血淋巴细胞与心肌组织中钙调神经磷酸酶信使核糖核酸水平相关性研究的初步报告[J]. 中国循环杂志, 2008, 23(2):113-116.
[11] Lin C C, Lin J L, Lin C S, et al. Activation of the calcineurin-nuclear factor of activated T cell signal transduction pathway in atrial fibrillation[J]. Chest, 2004, 126(6):1926-1932.
[12] Qi X Y, Yeh Y H, Xiao L, et al. Cellular signaling underlying atrial tachycardia remodeling of L-type calcium current[J]. Circ Res, 2008, 103(8):845-854.
[13] Saygili E, Rana O R, Meyer C, et al. The angiotensin-calcineurin-NFAT pathway mediates stretch-induced up-regulation of matrix metalloproteinases-2/-9 in atrial myocytes[J]. Basic Res Cardiol, 2009, 104(4):435-448.
[14] Bukowska A, Lendeckel U, Hirte D, et al. Activation of the calcineurin signaling pathway induces atrial hypertrophy during atrial fibrillation[J]. Cell Mol Life Sci, 2006, 63(3):333-342.
[15] Morin S, Charron F, Robitaille L, et al. GATA-dependent recruitment of MEF 2 proteins to target promoters[J]. EMBO J, 2000, 19(9):2046-2055.
[1] 魏金秋,张玉娇,李展,王曦敏,陈琳琳,杜娟娟,张勇,解新星,侯应龙. GCH1通过BH4通路对快速心房起搏犬自主神经重构的影响[J]. 山东大学学报(医学版), 2017, 55(5): 8-12.
[2] 李雁翔,张温花,杨飞龙,方量,徐忠华. 尿路上皮癌BRCA1基因与蛋白表达的相关性[J]. 山东大学学报(医学版), 2017, 55(5): 91-94.
[3] 刘童,张欣,王传新. IRX5 mRNA在结直肠癌诊断及预后中的价值[J]. 山东大学学报(医学版), 2016, 54(7): 69-74.
[4] 张洁,王爱红,董波,赵鹏. 原癌基因c-jun对毒胡萝卜素内酯处理的小鼠胚胎成纤维细胞生存率的影响[J]. 山东大学学报(医学版), 2016, 54(2): 44-48.
[5] 张凯, 梁飞, 韩波, 马晓春, 朱小龙, 张军, 张涛, 邹承伟. 同期射频消融改良迷宫Ⅲ术+心脏神经节丛消融术与单纯射频消融改良迷宫Ⅲ术治疗合并风湿性二尖瓣病变的心房颤动比较[J]. 山东大学学报(医学版), 2015, 53(5): 66-70.
[6] 李曼, 钟敬泉, 岳欣, 朱清, 郑兆通, 荣冰, 衣少雷, 谢飞, 张运. 环肺静脉电隔离术的不同消融终点对房颤患者预后的影响[J]. 山东大学学报(医学版), 2015, 53(3): 62-68.
[7] 张风雷, 郑曼, 张琦, 顾磊, 徐新生. 代谢综合征与P波离散度关系的探讨[J]. 山东大学学报(医学版), 2015, 53(2): 52-55.
[8] 陈静, 李春艳, 赵苗青, 崔京睛, 张娜, 傅艺冰. EZH2蛋白在卵巢上皮性肿瘤中的表达及其作用[J]. 山东大学学报(医学版), 2015, 53(2): 65-70.
[9] 吕岩红, 高海青, 邱洁. 达比加群酯预防非瓣膜性房颤患者血栓栓塞的有效性和安全性[J]. 山东大学学报(医学版), 2015, 53(11): 37-40.
[10] 张伶俐, 周莹, 李小荷, 李慧, 钟明, 张薇. 中国房颤人群心肌组织中MMPs与TIMPs的mRNA表达水平的Meta分析[J]. 山东大学学报(医学版), 2015, 53(1): 47-53.
[11] 韩波1,2,王建春2,张涛2,朱小龙2,李丛2,王正军2,赵勇2,邹承伟2. 风湿性心房颤动患者左心房组织中钙蛋白酶-2的表达[J]. 山东大学学报(医学版), 2014, 52(4): 93-96.
[12] 程显峰,梁飞,张骞,朱小龙,张海洲,张涛,韩波,邹承伟. 同期射频消融改良迷宫Ⅲ术+心脏神经节丛消融治疗心房颤动[J]. 山东大学学报(医学版), 2013, 51(2): 53-56.
[13] 郑少华1,张玉娇1,李志远2,侯绪娟3,王曦敏1,段文昌4,侯应龙1. 持续性快速右心房起搏犬肺静脉-左心房连接处自主神经重构的研究[J]. 山东大学学报(医学版), 2013, 51(12): 7-10.
[14] 付开丽1,张学义2,朱萌3,王志浩1,王华1,钟明1,张运1,张薇1. 不同病因心房颤动患者卒中危险的评估[J]. 山东大学学报(医学版), 2013, 51(06): 61-63.
[15] 孙雪林1,2,卜培莉1,刘军妮1,曹广庆3,李丽4,于琼4. 心房颤动患者心房组织SIRT1表达与心房纤维化的相关性[J]. 山东大学学报(医学版), 2012, 50(9): 68-72.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!