王梅香　殷屹崗　陳各才

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血漿抵抗素水平與心房顫動(dòng)關(guān)系的臨床研究

王梅香殷屹崗陳各才

目的通過(guò)測(cè)定血漿抵抗素的水平，研究其在孤立性心房顫動(dòng)(房顫)的發(fā)生與維持中的作用；同時(shí)分析影響其水平的相關(guān)因素及房顫的風(fēng)險(xiǎn)因素。方法 研究對(duì)象為2014年6月至12月因心悸等不適就診我院心內(nèi)科的患者140例，其中試驗(yàn)組為房顫人群，分為孤立性房顫(60例)和房顫合并高血壓(55例)；根據(jù)發(fā)病時(shí)間不同，孤立性房顫又分為陣發(fā)性與持續(xù)性房顫，各30例。正常對(duì)照組為正常人群，共25例。使用單因素方差分析比較房顫人群與正常人群血漿抵抗素水平的差異。用Pearson及多重線性回歸法分析影響房顫患者抵抗素水平的相關(guān)因素。用Logistic回歸分析影響房顫的風(fēng)險(xiǎn)因素。結(jié)果① 超敏C反應(yīng)蛋白(hs-CRP)及血漿抵抗素水平：所有房顫組的水平均高于對(duì)照組，其中孤立性房顫組低于房顫合并高血壓組；陣發(fā)性房顫組低于持續(xù)性房顫組。② Pearson相關(guān)分析：血漿抵抗素水平與hs-CRP水平、左房?jī)?nèi)徑大小及收縮壓均呈正相關(guān)(分別為r=0.530,P=0.000;r=0.265,P=0.004;r=0.364,P=0.000)。多重線性回歸分析進(jìn)一步顯示收縮壓(SBP)、hs-CRP水平與血漿抵抗素的水平存在線性關(guān)系：Y=-2.172+0.089 SBP+1.347 hs-CRP(R2=0.307，P<0.05)。③ Logistic回歸分析表明血漿抵抗素水平、hs-CRP水平均被納入回歸方程，且OR值均>1。結(jié)論① 血漿抵抗素水平孤立性房顫組明顯高于對(duì)照組，其中又以持續(xù)性房顫組增高為著，表明抵抗素與房顫的發(fā)生、節(jié)律的維持相關(guān)。② 血漿抵抗素水平與hs-CRP的水平呈正相關(guān)，間接表明房顫的發(fā)生可能與抵抗素具有某種炎性特質(zhì)相關(guān)，提示抵抗素可引起炎癥反應(yīng)并和炎癥介質(zhì)一起參與了房顫發(fā)生、維持。③ 血漿抵抗素水平在房顫合并高血壓患者中升高明顯，且具有協(xié)同效應(yīng)，提示抵抗素也許具有獨(dú)立表達(dá)高血壓與房顫疾病的潛質(zhì)。同時(shí)本研究也證實(shí)了高血壓為房顫的風(fēng)險(xiǎn)因素，可推測(cè)抵抗素通過(guò)高血壓影響房顫。

心房顫動(dòng)；血漿抵抗素；炎癥

抵抗素是一種分泌型的蛋白，且半胱氨酸殘基含量較高。人的抵抗素主要由單核巨噬細(xì)胞分泌而來(lái)。研究發(fā)現(xiàn)動(dòng)脈粥樣硬化、冠心病及高血壓患者血漿的抵抗素普遍升高[1]，并推測(cè)其可能與胰島素的抵抗有關(guān)，認(rèn)為抵抗素也許是聯(lián)系炎癥與胰島素抵抗的紐帶，從而參與冠心病、高血壓等疾病的發(fā)生、發(fā)展[2]。目前，眾多研究證實(shí)了抵抗素與炎癥存在關(guān)系，且與超敏C反應(yīng)蛋白(hs-CRP)的水平呈正性相關(guān)[3]。最新2016年ESC房顫管理指南對(duì)房顫進(jìn)行了臨床分類(lèi)，包括繼發(fā)于結(jié)構(gòu)性心臟病的房顫、局灶性房顫、多基因房顫、術(shù)后房顫、二尖瓣狹窄和人工心臟瓣膜相關(guān)房顫、運(yùn)動(dòng)員房顫和單基因房顫等類(lèi)型。本研究試驗(yàn)組為孤立性房顫患者，是指房顫發(fā)生在無(wú)基礎(chǔ)心臟病變的中青年，且臨床相關(guān)檢查未發(fā)現(xiàn)心房明顯擴(kuò)大、心功能不全及相關(guān)的心外疾病。目前關(guān)于房顫的具體機(jī)制仍不確定。Anné等[4]報(bào)道房顫的發(fā)生及維持與心房?jī)?nèi)徑增大導(dǎo)致結(jié)構(gòu)重構(gòu)和電重構(gòu)有關(guān)聯(lián)，主要機(jī)制包括心房臨界物質(zhì)增多，心房擴(kuò)大導(dǎo)致機(jī)械-電反饋，細(xì)胞外基質(zhì)變性、纖維化，神經(jīng)內(nèi)分泌改變等。近年來(lái)，眾多研究都支持炎癥作用于房顫的發(fā)生與維持，但多數(shù)是hs-CRP水平與房顫關(guān)系的相關(guān)報(bào)道[5]。本研究分析了抵抗素直接通過(guò)其炎性特質(zhì)及其對(duì)相關(guān)風(fēng)險(xiǎn)因素的間接作用參與房顫的發(fā)生及發(fā)展。

1　資料與方法

1.1一般資料

2014年6月至12月因心悸就診于泰州市人民醫(yī)院心內(nèi)科的患者，共入選140例(男72/女68)，平均(54.45±6.10)歲。其中25例為正常對(duì)照組(男12/女13)，平均(55.28±7.28)歲;孤立性房顫組60例(男32/女28),平均(53.42±5.00)歲，其中陣發(fā)性房顫及持續(xù)性房顫患者各30例；另外55例為房顫合并高血壓組(男28/女27)，平均(55.20±6.55)歲。

1.2方法

體質(zhì)量指數(shù)=體質(zhì)量(kg)/身高2(m2)；連續(xù)測(cè)量?jī)纱尾煌瑫r(shí)間的肱動(dòng)脈血壓水平，取其平均值；采用酶法(日立生化分析儀)測(cè)定空腹靜脈血糖、低密度脂蛋白、三酰甘油、高密度脂蛋白及總膽固醇。左房?jī)?nèi)徑通過(guò)二維超聲在胸骨旁的左室長(zhǎng)軸切面測(cè)定。hs-CRP水平采用免疫放射比濁法測(cè)定。

血漿抵抗素水平的測(cè)定：采取空腹靜脈血，通過(guò)離心( 3 000 r/min，離心15 min)收集血漿0.5 mL，并置于-80℃的冰箱中保存待檢，所有標(biāo)本保存未超過(guò)6個(gè)月；用人抵抗素定量試劑盒(大連泛邦化工技術(shù)開(kāi)發(fā)有限公司)采用ELISA法測(cè)定血漿抵抗素的濃度：① 向預(yù)先包被抵抗素抗體的包被微孔中依次加入標(biāo)本、標(biāo)準(zhǔn)品、HRP標(biāo)記的檢測(cè)抗體，經(jīng)過(guò)溫育及徹底洗滌；② 用底物TMB顯色，TMB在過(guò)氧化物酶的催化下轉(zhuǎn)化成藍(lán)色，并在酸作用下最終轉(zhuǎn)換成黃色；其顏色的深淺和樣品中抵抗素濃度呈正相關(guān)；③ 用酶標(biāo)儀在450 nm波長(zhǎng)下測(cè)定吸光度；④ 計(jì)算機(jī)繪出標(biāo)準(zhǔn)品的標(biāo)準(zhǔn)曲線，根據(jù)樣品的吸光度讀出相應(yīng)的濃度，再乘以稀釋倍數(shù)(×5)，即為所測(cè)樣品的實(shí)際濃度。

1.3統(tǒng)計(jì)學(xué)分析

2　結(jié)果

2.1血漿抵抗素及hs-CRP的水平比較

血漿抵抗素及hs-CRP水平房顫組均高于正常對(duì)照組(P<0.05，P<0.01)；持續(xù)性房顫組高于陣發(fā)性房顫組(P<0.05)；而且房顫合并高血壓組高于孤立性房顫組(P<0.05，P<0.01)，差異均有統(tǒng)計(jì)學(xué)意義。見(jiàn)表1。

表1　正常對(duì)照組、孤立性房顫組與房顫合并高血壓組血漿抵抗素及hs-CRP水平的比較

a：與正常對(duì)照組相比，P<0.01；b：與陣發(fā)性房顫組相比，P<0.05；c：與孤立性房顫組相比，P<0.05

2.2Pearson相關(guān)分析

將血漿抵抗素水平分別與hs-CRP水平、左房?jī)?nèi)徑及收縮壓進(jìn)行相關(guān)性分析，結(jié)果分別為r=0.530,P=0.000；r=0.265,P=0.004；r=0.364,P=0.000，均呈正相關(guān)。見(jiàn)圖1。

2.3多重線性回歸分析

血漿抵抗素水平與收縮壓(SBP)、hs-CRP水平呈線性關(guān)系：Y=-2.172+0.089 SBP+1.347 hs-CRP(R2=0.307，P<0.05)。見(jiàn)表2。

圖1　血漿抵抗素與hs-CRP水平的相關(guān)性

變量偏回歸系數(shù)標(biāo)準(zhǔn)誤標(biāo)準(zhǔn)偏回歸系數(shù)t值P值常數(shù)項(xiàng)-2.1725.390—-0.4030.688收縮壓0.0890.0440.1782.0220.046

續(xù)表

2.4二分類(lèi)Logistic分析(向前逐步回歸法)

以房顫的有無(wú)為應(yīng)變量，一般測(cè)量指標(biāo)(年齡、性別、膽固醇、血壓、血糖等)、左房?jī)?nèi)徑、hs-CRP及血漿抵抗素水平為自變量。結(jié)果顯示SBP、左房?jī)?nèi)徑、血漿抵抗素及hs-CRP水平進(jìn)入回歸模型，且均有統(tǒng)計(jì)學(xué)意義(P<0.05)。而且結(jié)果顯示它們的OR值均>1。

表3　以房顫有無(wú)為應(yīng)變量的Logistic回歸分析

3　討論

本研究顯示，血漿抵抗素水平在持續(xù)性房顫患者中高于陣發(fā)性房顫患者，且高于正常人群，提示抵抗素與房顫節(jié)律的維持及其發(fā)生存在關(guān)系，但目前尚無(wú)相關(guān)的大量臨床研究直接報(bào)道，有待繼續(xù)追蹤證實(shí)。另外，本研究還顯示hs-CRP存在于孤立性房顫組(持續(xù)性與陣發(fā)性)的濃度均高于正常對(duì)照組，同時(shí)持續(xù)性房顫患者的濃度高于陣發(fā)性房顫患者，考慮炎癥反應(yīng)與房顫的發(fā)生和節(jié)律維持相關(guān)，結(jié)果與Hagiwara[6]及Chung等[7]的研究相符。

研究還顯示，血漿抵抗素水平與收縮壓呈正相關(guān)，且多重線性回歸也顯示抵抗素水平與收縮壓存在線性關(guān)系，提示高血壓與抵抗素水平存在著密切的聯(lián)系。這與Takata等[8]及Zhang等[9]的研究相一致。房顫合并高血壓患者的血漿抵抗素水平較單純房顫患者的明顯升高，且具有協(xié)同效應(yīng)，提示高血壓與房顫這兩者可能相互獨(dú)立作用于血漿的抵抗素水平，從而推測(cè)抵抗素水平可能具有獨(dú)立表達(dá)高血壓與房顫這兩種疾病的潛質(zhì)。同時(shí)，本研究也證實(shí)了高血壓為房顫的風(fēng)險(xiǎn)因素，可推測(cè)抵抗素通過(guò)高血壓導(dǎo)致房顫的發(fā)生。

研究中兩種線性關(guān)系分析表明血漿抵抗素水平與hs-CRP水平、左房?jī)?nèi)徑呈正相關(guān)，間接表明房顫的發(fā)生可能與抵抗素具有炎癥性質(zhì)相關(guān)，提示抵抗素可能引起炎癥反應(yīng)并和炎癥介質(zhì)一起參與了房顫的發(fā)生、維持。并且血漿抵抗素水平與hs-CRP水平都被納入了Logistic回歸模型，且兩者的OR值均>1，提示兩者均是房顫的重要風(fēng)險(xiǎn)因素，說(shuō)明兩者增高的患者發(fā)生房顫的概率高于正常人。這與Rienstra等[10]及Gungor等[11]的發(fā)現(xiàn)相符。

綜上，本研究發(fā)現(xiàn)抵抗素可以作為新的炎癥介質(zhì)之一，它通過(guò)與其他各種炎性因子(氧化亞氮、白介素、緩激肽及腫瘤壞死因子等)共同參與NF-κB信號(hào)通路及其自身mRNA的表達(dá)，進(jìn)入了系統(tǒng)性炎癥反應(yīng)的惡性循環(huán)，導(dǎo)致心房的內(nèi)徑變大和電紊亂，從而促進(jìn)房顫的發(fā)生與發(fā)展；也可以通過(guò)影響房顫的多個(gè)風(fēng)險(xiǎn)因素(高血壓、肥胖、冠心病及心衰等)，間接參與房顫的發(fā)生與維持。所以推測(cè)抵抗素會(huì)在不久的將來(lái)成為房顫的早期預(yù)測(cè)因子，聯(lián)合動(dòng)態(tài)監(jiān)測(cè)病情的發(fā)展與轉(zhuǎn)歸，進(jìn)而改善患者預(yù)后。

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Clinical study on the relationship between plasma resistin level and atrial fibrillation

WangMei-xiang,YinYi-gang,ChenGe-cai

(Department of Cardiology, Jiangsu Taizhou People’s Hospital, Taizhou Jiangsu 225300, China)

ObjectiveBy measuring the level of plasma resistin, to study its roles in the occurrence and maintenance of lone atrial fibrillation(LAF), and analyze the related influential factors of plasma resistin level and risk factors of AF. MethodsResearch objects were 140 patients consulting in the department of cardiology of our hospital because of palpitation from June to December in 2014. The experimental group consisted of AF patients who were classified into patients with LAF(60 cases) and those with AF complicating hypertension(55 cases), respectively. The LAF cases were further divided into paroxysmal AF group and persistent AF group, each with 30 cases. In the control group were normal people(25 cases). The difference of plasma resistin level was analyzed between AF patients and normal people by one-way abalysis of variance, and its related influential factors for AF patients were analyzed in methods of Pearson correlation analysis and multiple linear regression. Logistic regression was applied in analyzing risk factors of AF. Results(i) In terms of high sensitive C reactive protein( hs-CRP) and plasma resistin level, the levels of AF group were all higher than those of control group; among the AF patients, the levels of LAF group were lower than those of AF complicating hypertension group and the levels of paroxysmal AF group were lower than those of persistent AF group. (ii) Pearson correlation analysis showed that plasma resistin level was positively correlated with hs-CRP level(r=0.530,P=0.000), left atrial diameter(r=0.265,P=0.004) and systolic blood pressure(SBP)(r=0.364,P=0.000). Multiple linear regression analysis further revealed that there was a linear relationship among SBP, hs-CRP and plasma vesistin levels:Y=-2.172+0.089 SBP+1.347 hs-CRP(R2=0.307,P<0.05). (iii) Logistic regression analysis indicated that plasma resistin and hs-CRP levels were both enrolled into the regression equation, withOR>1. Conclusion(i) The level of plasma resistin in LAF group was significantly higher than that in control group, especially the cases in persistent AF group, which indicated that resistin participated in the occurrence and maintenance of AF. (ii) Plasma resistin level was positively correlated with hs-CRP level. It implied that the occurrence of AF may be related with some inflammatory characteristics of resistin, which suggested that resistin could give rise to inflammatory reaction and participate in the occurrence and maintenance of AF with inflammatory mediators. (iii) Plasma resistin level increased significantly in AF patients complicating hypertension and showed synergistic effect, which suggested possible potentiality of resistin in expressing hypertension and AF independently. Meanwhile, the study also demonstates that hypertension is a risk factor of AF. It might be suspected that resistin can impact on AF via hypertension.

atrial fibrillation; plasma resistin; inflammation

225300 江蘇 泰州，泰州市人民醫(yī)院心內(nèi)科

王梅香，住院醫(yī)師，主要從事心臟電生理方向的研究，E-mail：569896951@qq.com

10.13308/j.issn.2095-9354.2016.05.013

2016-09-07)(本文編輯：郭欣)

R541.7

A

2095-9354(2016)05-0359-04