龐建仿
(天津市寧河縣醫(yī)院急診科,天津 301500)
急性心肌梗死患者血清S100A1表達(dá)及臨床意義
龐建仿
(天津市寧河縣醫(yī)院急診科,天津 301500)
目的:探討急性心肌梗死(acute myocardial infarction,AMI)患者血清S100A1表達(dá)及臨床意義。方法:選擇2011年1月至2013年12月收治的AMI患者86例和健康對(duì)照30例,采用酶聯(lián)免疫吸附試驗(yàn)(ELISA)法檢測(cè)血清S100A1和血漿肌鈣蛋白Ⅰ(cardiac troponinⅠ,cTnⅠ)水平;采用熒光免疫方法檢測(cè)血清高敏C-反應(yīng)蛋白(high-sensitivity C reactive protein,hs-CRP)和血清肌酸激酶同工酶(creatine kinase-MB,CK-MB)水平。結(jié)果:AMI組患者血清S100A1、hs-CRP、cTnⅠ、CK-MB水平明顯高于對(duì)照組(P<0.01)。血清S100A1水平與hs-CRP、cTnⅠ、CK-MB呈正相關(guān)(P<0.01或0.05)。AMI患者發(fā)病初期血清S100A1水平持續(xù)升高,受試者工作特征曲線(xiàn)分析結(jié)果顯示,曲線(xiàn)下面積為0.855(95%CI:0.814~0.889),以S100A1水平114 μg/L為臨界值,診斷靈敏度為94.7%,特異度為88.9%。結(jié)論:血清S100A1在AMI初期迅速持續(xù)的升高,對(duì)AMI診斷敏感度性和特異度高,作為新的血清學(xué)指標(biāo)在AMI早期診斷中有重要參考價(jià)值。
急性心肌梗死;S100A1;早期診斷
多項(xiàng)血清酶學(xué)指標(biāo)在急性心肌梗死(acute myocardial infarction,AMI)診斷、鑒別診斷、療效評(píng)價(jià)和預(yù)后估計(jì)等方面的應(yīng)用價(jià)值已被公認(rèn)[1],但也其敏感性和特異性較差,不能及早診斷。有研究說(shuō)明血漿中心肌特異的miRNAs可能作為一個(gè)潛在的AMI的生物標(biāo)志物[2-3]。心臟生化標(biāo)志物檢測(cè),目前以蛋白質(zhì)為主的標(biāo)志物越來(lái)越受到重視,如肌鈣蛋白Ⅰ(cardiac troponinⅠ,cTnⅠ)或肌紅蛋白異常為AMI診斷必備條件之一,也存在局限性[4-6]。鈣結(jié)合蛋白S100A1是S100蛋白家族成員成員之一,是心肌收縮、舒張功能最重要的調(diào)節(jié)因子[7-8]。有研究發(fā)現(xiàn)S100A1在AMI患者可作為缺血性冠狀動(dòng)脈疾病的早期診斷標(biāo)志物[9]。文本旨在探討AMI患者血清S100A1表達(dá)及臨床意義。
1.1 一般資料 選擇2011年1月至2013年12月本院收治的AMI患者86例,其中男45例,女41例;年齡38~65歲,平均(54.16±11.32)歲?;颊咴\斷標(biāo)準(zhǔn)符合中華醫(yī)學(xué)會(huì)心血管病分會(huì)2001年修訂的AMI診斷和治療指南[10]。其中12例患者合并心源性休克?;颊呔鶡o(wú)肝腎疾病、出凝血性疾病、內(nèi)分泌疾病、惡性腫瘤及感染等疾病。所有患者進(jìn)行溶栓治療或經(jīng)皮冠狀動(dòng)脈腔內(nèi)血管成形術(shù)治療。另選擇健康體檢者30例作為對(duì)照組。2組在年齡、性別上差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)?;颊呋蚣覍倬炇鹬橥鈺?shū)。
1.2 方法
1.2.1 血清S100A1水平檢測(cè) 采集患者發(fā)病后1、5、10、15、20、25、30、35 h的外周血5 ml,采用S100 Calcium Binding Protein A1(S100A1)酶聯(lián)免疫吸附試驗(yàn)(ELISA)試劑盒(上海聯(lián)世生物科技有限公司)檢測(cè)血清中S100A1水平,嚴(yán)格按照說(shuō)明書(shū)操作方法進(jìn)行。同時(shí)檢測(cè)對(duì)照組血清S100A1水平。
1.2.2 其他生物指標(biāo)的檢測(cè) 抽取2組研究對(duì)象靜脈血,采用熒光免疫方法檢測(cè)血清高敏C-反應(yīng)蛋白(high-sensitivity C reactive protein,hs-CRP)和血清肌酸激酶同工酶(creatine kinase-MB,CKMB)水平;采用ELISA法檢測(cè)血漿cTnⅠ水平。
1.3 統(tǒng)計(jì)學(xué)方法 采用SPSS 16.0統(tǒng)計(jì)軟件對(duì)數(shù)據(jù)進(jìn)行t檢驗(yàn)、相關(guān)性分析。通過(guò)受試者工作特征曲線(xiàn)(receiver operator characteristic curve,ROC)判斷S100A1水平在AMI診斷中的靈敏度和特異度。P<0.05為差異有統(tǒng)計(jì)學(xué)意義。
2.1 AMI組與對(duì)照組血清S100A1、hs-CRP、cTnⅠ、CK-MB水平比較及其相關(guān)性分析 與對(duì)照組比較,AMI組患者血清S100A1、hs-CRP、cTnⅠ、CK-MB水平明顯升高(P<0.01),見(jiàn)表1。血清S100A1水平與hs-CRP、cTnⅠ、CK-MB呈正相關(guān),見(jiàn)表2。
表1 AMI組與對(duì)照組血清S100A1、hs-CRP、cTnⅠ和CK-MB水平比較(±s)
表1 AMI組與對(duì)照組血清S100A1、hs-CRP、cTnⅠ和CK-MB水平比較(±s)
組別nS100A1(ng/L)hs-CRP(mg/L)cTnⅠ(mg/L)CK-MB(U/L)對(duì)照組3058.3±17.32.77±1.060.33±0.1415.71±4.54 AMI組86351.3±281.28.22±1.645.57±1.4191.88±16.98 t值4.222.245.123.14 P值0.0040.0060.0010.005
表2 血清S100A1與相關(guān)生物標(biāo)記物在AMI的相關(guān)性分析
2.2 AMI患者發(fā)病不同時(shí)間點(diǎn)血清S100A1水平
AMI患者發(fā)病不同時(shí)間點(diǎn)血清S100A1水平是一個(gè)動(dòng)態(tài)變化的過(guò)程,在發(fā)病1 h內(nèi)顯著持續(xù)的升高,在10 h時(shí)達(dá)最高,15 h后顯著下降,20 h后下降速度緩慢。見(jiàn)圖1。
2.3 AMI血清S100A1水平的診斷價(jià)值 ROC分析結(jié)果顯示,曲線(xiàn)下面積(AUC)為0.855(95% CI:0.814~0.889),見(jiàn)圖2。根據(jù)ROC分析,ROC分析確定了最佳S100A1水平的臨界值為114 μg/L,診斷靈敏度為94.7%,特異度為88.9%。提示這血清S100A1水平作為AMI的生物標(biāo)志物均有一定的準(zhǔn)確性和可行性。
圖2 血清S100A1水平診斷AMI的ROC曲線(xiàn)
隨著冠心病的逐漸增多,AMI的發(fā)病率也明顯提高,隨之死亡率也逐年攀升,因此對(duì)患者早期診斷是挽救患者生命、提高患者生存質(zhì)量的重要手段。
S100A1的表達(dá)有高度的組織特異性和細(xì)胞特異性,在骨骼肌中很少表達(dá),而在健康心肌細(xì)胞中則大量表達(dá),其中以左心室為主,右心室和心房表達(dá)較少[11]。S100A1在右心室肥大時(shí)上調(diào),心衰末期則下調(diào),提示S100A1的表達(dá)與心肌的收縮能力有關(guān),它通過(guò)對(duì)肌漿網(wǎng)鈣ATP酶、蘭尼堿受體的調(diào)控,調(diào)節(jié)心肌細(xì)胞Ca2+的釋放、攝取、轉(zhuǎn)運(yùn),是心肌收縮、舒張功能最重要的調(diào)節(jié)因子[12-13]。有研究發(fā)現(xiàn)在急性心肌缺血時(shí)血漿中S100A1升高,認(rèn)為S100A1可作為急性心肌缺血的早期標(biāo)志[9]。
AMI的發(fā)病及調(diào)節(jié)機(jī)制復(fù)雜,涉及多種基因、蛋白因子和酶的調(diào)節(jié)。hs-CRP、cTnⅠ、CK-MB在AMI的發(fā)生發(fā)展過(guò)程的變化的較為明確,在臨床診斷及預(yù)后判斷中起到一定的作用[14-16]。本研究檢測(cè)AMI患者血清S100A1水平發(fā)現(xiàn),S100A1水平明顯高于對(duì)照組。而且通過(guò)相關(guān)性分析發(fā)現(xiàn),血清S100A1水平與hs-CRP、cTnⅠ、CK-MB水平呈正相關(guān)。因患者治療方式以及病例數(shù)量少等因素存在,這種直接或間接的相關(guān)性及其機(jī)制尚待進(jìn)一步的研究。
本研究發(fā)現(xiàn)AMI患者發(fā)病不同時(shí)間點(diǎn)血清S100A1水平是一個(gè)動(dòng)態(tài)變化的過(guò)程,在發(fā)病1 h內(nèi)顯著持續(xù)的升高,在10 h時(shí)達(dá)最高,15 h后顯著下降,20 h后下降速度緩慢。在發(fā)病初期,S100A1水平急速持續(xù)的上升是一個(gè)重要特征。同時(shí)ROC分析結(jié)果顯示,AUC為0.855(95%CI:0.814~0.889)。根據(jù)ROC分析,ROC分析確定了最佳S100A1水平的臨界值為114 μg/L,診斷靈敏度為94.7%,特異度為88.9%。這提示血清S100A1水平作為AMI的生物標(biāo)志物均有一定的準(zhǔn)確性和可行性。
綜上所述,血清S100A1在AMI初期迅速持續(xù)的升高,對(duì)AMI診斷敏感度和特異度高,與常用生物標(biāo)記物hs-CRP、cTnⅠ、CK-MB變化呈正相關(guān),可作為新的血清學(xué)指標(biāo)在AMI早期診斷中有重要參考價(jià)值。
[1]Kruse JM,Enghard P,Sch?der T,et al.Weak diagnostic performance of troponin,creatine kinase and creatine kinase-MB to diagnose or exclude myocardial infarction after successful resuscitation[J].Int J Cardiol.2014,173(2):216-221.
[2]D'Alessandra Y,Devanna P,Limana F,et al.Circulating microRNAs are new and sensitive biomarkers of myocardial infarction[J].Eur Heart J,2010,31(22):2765-2773.
[3]Adachi T,Nakanishi M,Otsuka Y,et al.Plasma microRNA 499 as a biomarker of acute myocardial infarction[J].Clin Chem,2010,56(7):1183-1185.
[4]Wang YR,Guo ZB,Huang LP.Value of different biochemical markers in early diagnosis of acute myocardial infarction[J].Nan Fang Yi Ke Da Xue Xue Bao,2014,34(9):1347-1350.
[5]Wang XH,Liu SQ,Wang.Correlation of serum high-sensitivity C-reactive protein and interleukin-6 in patients with acute coronary syndrome[J]Y Genet Mol Res,2014,13(2):4260-4266.
[6]Wildi K,Reichlin T,Twerenbold R,et al.Serial changes in high-sensitivity cardiac troponin I in the early diagnosis of acute myocardial infarction[J].Int J Cardiol,2013,168(4):4103 -4110.
[7]Most P,Seifert H,Gao E,et al.Cardiac S100A1protein levels determine contractile performance and propensity toward heart failureaftermyocardialinfarction[J].Circulation,2006,114(12):1258-1268.
[8]Pleger ST,Remppis A,Heidt B,et al.S100A1 gene therapy preserves in vivo cardiac function after myocardial infarction[J].Mol Ther,2005,12(6):1120-1129.
[9]Kiewitz R,Acklin C,Minder E,et al.S100A1,a newmarker for acute myocardial ischemia[J].Biochem Biophys Res Commun,2000,274(3):865-871.
[10]中華醫(yī)學(xué)會(huì)心血管病學(xué)分會(huì)中華心血管病雜志編輯委員會(huì)中國(guó)循環(huán)雜志編輯委員會(huì).急性心肌梗死診斷和治療指南[J].中華心血管病雜志,2001,29(12):705-720.
[11]Zimmer DB,Cornwall EH,Landar A,et al.The S100 protein family:history,function,and expression[J].Brain Res Bull,1995,37(4):417-429.
[12]Duarte-Costa S,Castro-Ferreira R,Neves JS,et al.S100A1:a major player in cardiovascular performance[J].Physiol Res,2014,63(6):669.
[13]Bennett MK,Sweet WE,Baicker-McKee S,et al.S100A1 in human heart failure:lack of recovery following left ventricular assist device support[J].Circ Heart Fail,2014,7(4):612-618.
[14]Wei S,Mao L,Liu B,et al.Serum biomarkers and the prognosis of AMI patients[J].Herz,2014,39(3):384-389.
[15]Palamalai V,Murakami MM,Apple FS.Diagnostic performance of four point of care cardiac troponin I assays to rule in and rule out acute myocardial infarction[J].Clin Biochem,2013,46(16-17):1631-1635.
[16]Kavsak PA,MacRae AR,Newman AM,et al.Effects of contemporary troponin assay sensitivity on the utility of the early markers myoglobin and CKMB isoforms in evaluating patients with possible acute myocardial infarction[J].Clin Chim Acta,2007,380(1-2):213-216.
The Serum Level of S100A1 in Patients with Acute Myocardial Infarction and Its Clinical Significance
PANG Jianfang
(Emergency Department of Ninghe Hospital of Tianjin,Tianjin 301500,China)
Objective:To investigate the serum levels of S100A1 in patients with acute myocardial infarction(AMI)and its clinical significance.Methods:The level of serum S100A1 and plasma cardiac troponinⅠ(cTnⅠ)level in 86 patients with AMI and 30 control volunteers were detected by ELISA,and serum high-sensitivity C reactive protein(hs-CRP)and creatine kinase-MB(CK-MB)were detected by fluorescence immunoassay.Results:The levels of S100A1,hs-CRP,cTnⅠand CK-MB in patients with AMI group were significantly higher than those in the control group(P<0.01).A significant positive correlation was found between the serum level of S100A1with hs-CRP,cTnⅠ,CK-MB(P<0.01 or 0.05).Serum S100A1 level continued to rise in the early onset of AMI.ROC analysis showed that the area under the curve(AUC)was 0.855(95%CI:0.814-0.889),the best S100A1 critical level was 114 μg/L,the diagnostic sensitivity was 94.7%and the specificity was 88.9%.Conclusions:Serum S100A1 rapid sustained elevates in the early of AMI.It is high sensitivity and specificity for diagnosis of AMI,and it can be used as a new serological indexes in the diagnosis of early AMI,and it has an important reference value.
acute myocardial infarction;S100A1;early diagnosis
R541.4
A
1008-2344(2015)02-0094-03 doi:10.3969/j.issn.1008-2344.2015.02.011
2015-01-15