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    急性ST段抬高型心肌梗死患者血清miR-1-3p、H-FABP水平變化及臨床意義

    2020-04-20 10:40:46張榮峰李丹娜董穎雪
    關(guān)鍵詞:心肌梗死心功能我院

    張榮峰 李丹娜 董穎雪

    [摘要] 目的 探討急性ST段抬高型心肌梗死(STEMI)患者血清miR-1-3p、心臟型脂肪酸結(jié)合蛋白(H-FABP)的表達(dá),并分析二者對(duì)STEMI的診斷價(jià)值。 方法 選取2016年12月~2019年6月在大連醫(yī)科大學(xué)附屬第一醫(yī)院(以下簡(jiǎn)稱(chēng)“我院”)診治的120例STEMI患者為STEMI組,另選取同期我院120例心功能正常者為非STEMI組。采用實(shí)時(shí)熒光定量PCR法檢測(cè)血清miR-1-3p表達(dá),采用酶聯(lián)免疫吸附法檢測(cè)血清H-FABP、N端腦鈉肽前體(NT-proBNP)水平,采用全自動(dòng)生化分析儀檢測(cè)總膽固醇(TC)、低密度脂蛋白膽固醇(LDL-C)、三酰甘油(TG)水平;采用彩色超聲診斷儀測(cè)量左室射血分?jǐn)?shù)(LVEF)、左室舒張末期內(nèi)徑(LVEDD)。采用Pearson相關(guān)性分析STEMI患者血清miR-1-3p、H-FABP與脂代謝指標(biāo)、心功能指標(biāo)的相關(guān)性;并采用受試者操作特征曲線(xiàn)(ROC)分析血清miR-1-3p、H-FABP及聯(lián)合檢測(cè)STEMI的診斷價(jià)值。 結(jié)果 STEMI組血清miR-1-3p表達(dá)及LVEF低于非STEMI組,血清H-FABP、TC、LDL-C、NT-proBNP水平及LVEDD高于非STEMI組,差異均有統(tǒng)計(jì)學(xué)意義(均P < 0.05)。兩組血清TG比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P > 0.05)。STEMI組血清miR-1-3p與TC、LDL-C、NT-proBNP、LVEDD、H-FABP均呈負(fù)相關(guān)(r < 0,P < 0.05),與LVEF呈正相關(guān)(r > 0,P < 0.05);血清H-FABP與TC、LDL-C、NT-proBNP、LVEDD均呈正相關(guān)(r > 0,P < 0.05),與LVEF、miR-1-3p呈負(fù)相關(guān)(r < 0,P < 0.05);二者與TG均無(wú)明顯相關(guān)性(P > 0.05)。ROC分析顯示,血清miR-1-3p、H-FABP對(duì)STEMI均有一定的診斷價(jià)值,二者聯(lián)合檢測(cè)的診斷價(jià)值高于單獨(dú)檢測(cè)[AUC=0.815,95%CI(0.728~0.846)]。 結(jié)論 STEMI患者血清miR-1-3p呈低表達(dá),H-FABP呈高表達(dá),二者均與患者的脂代謝指標(biāo)、心功能指標(biāo)存在一定的相關(guān)性,二者聯(lián)合檢測(cè)可進(jìn)一步提高對(duì)STEMI的診斷價(jià)值。

    [關(guān)鍵詞] 急性ST段抬高型心肌梗死;miR-1-3p;心臟型脂肪酸結(jié)合蛋白;診斷價(jià)值

    [中圖分類(lèi)號(hào)] R542.22? ? ? ? ? [文獻(xiàn)標(biāo)識(shí)碼] A? ? ? ? ? [文章編號(hào)] 1673-7210(2020)03(c)-0168-05

    [Abstract] Objective To investigate the expression of serum miR-1-3p and Heart-type fatty acid binding protein (H-FABP) in patients with acute ST-segment elevation myocardial infarction (STEMI), and to analyze the diagnostic value of both to STEMI. Methods A total of 120 STEMI patients treated in the First Affiliated Hospital of Dalian Medical University (hereinafter referred to as “our hospital”) from December 2016 to June 2019 were selected as the STEMI group, and another 120 patients with normal cardiac function in our hospital during the same period were selected as the non-STEMI group. The expression of serum miR-1-3p was detected by real-time fluorescence quantitative PCR. Serum levels of H-FABP and N-terminal pro B-type natriuretic peptide (NT-proBNP) were determined by enzyme-linked immunosorbent assay. The levels of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and triacylglycerol (TG) were measured by automatic biochemical analyzer. Left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD) were measured by color ultrasound diagnostic instrument. Pearson correlation was used to analyze the correlation of serum miR-1-3p and H-FABP with lipid metabolism index and cardiac function index in STEMI patients. The diagnostic value of serum miR-1-3p, H-FABP and combined detection of STEMI was analyzed by using the receiver operating characteristic curve (ROC). Results Serum miR-1-3p expression and LVEF in the STEMI group were lower than those in the non-STEMI group, and the levels of serum H-FABP, TC, LDL-C, NT-proBNP and LVEDD in STEMI group were higher than those in the non-STEMI group, with statistically significant differences (all P < 0.05). There was no significant difference in serum TG between the two groups (P > 0.05). Serum miR-1-3p in STEMI group was negatively correlated with TC, LDL-C, NT-proBNP, LVEDD, and H-FABP (r < 0, P < 0.05), and positively correlated with LVEF (r > 0, P < 0.05). Serum H-FABP was positively correlated with TC, LDL-C, NT-proBNP and LVEDD (r > 0, P < 0.05), and negatively correlated with LVEF and miR-1-3p (r < 0, P < 0.05). There was no significant correlation between them and TG (P > 0.05). ROC analysis showed that serum miR-1-3p and H-FABP had certain diagnostic value for STEMI, and the diagnostic value of the combined detection was higher than that of the single detection [AUC=0.815, 95%CI (0.728-0.846)]. Conclusion Serum miR-1-3p was low expressed and H-FABP was high expressed in STEMI patients, both of which were correlated with lipid metabolism index and cardiac function index of the patients to some extent. The combined detection of the two could further improve the diagnostic value of STEMI.

    [Key words] Acute ST-segment elevation myocardial infarction; MiR-1-3p; Heart-type fatty acid binding protein; Diagnostic value

    急性ST段抬高型心肌梗死(STEMI)主要由冠狀動(dòng)脈斑塊破裂、裂隙或夾層引起冠狀動(dòng)脈血供障礙,進(jìn)而導(dǎo)致心肌細(xì)胞出現(xiàn)缺血、缺氧的狀態(tài),且心電圖表現(xiàn)為ST段抬高[1]。微小核糖核酸(miRNA)是內(nèi)源性非編碼RNA,參與基因轉(zhuǎn)錄后水平的調(diào)控,具有廣泛的生物學(xué)功能,近年來(lái)有大量研究顯示多種miRNA可能參與了STEMI的發(fā)生、發(fā)展,如miR-30d、miR-423-5p[2]等。miR-1-3p是一種與多種惡性腫瘤進(jìn)展密切相關(guān)的miRNA[3-4],近年來(lái)有研究顯示其與心血管疾病的發(fā)生、發(fā)展密切相關(guān),如Li等[5]的研究證實(shí)miR-1-3p可能通過(guò)靶向電壓門(mén)控氯通道3來(lái)影響肥厚型心肌病的疾病進(jìn)展。心臟型脂肪酸結(jié)合蛋白(H-FABP)是由132個(gè)氨基酸構(gòu)成的可溶性蛋白質(zhì),近年來(lái)的研究顯示[6],H-FABP可作為心肌損傷的新型標(biāo)志物,對(duì)急性冠脈綜合征患者的預(yù)后有重要的評(píng)估價(jià)值。目前鮮有miR-1-3p、H-FABP與STEMI相關(guān)的研究。本研究旨在探討STEMI患者血清miR-1-3p、H-FABP的表達(dá)情況,并進(jìn)一步分析了二者與患者脂代謝指標(biāo)、心功能指標(biāo)的關(guān)系以及其對(duì)STEMI的診斷價(jià)值,現(xiàn)報(bào)道如下:

    1 資料與方法

    1.1 一般資料

    選取2016年12月~2019年6月在大連醫(yī)科大學(xué)附屬第一醫(yī)院(以下簡(jiǎn)稱(chēng)“我院”)接受治療的STEMI患者120例作為STEMI組,納入標(biāo)準(zhǔn):①診斷標(biāo)準(zhǔn)參考我國(guó)2015版《急性ST段抬高型心肌梗死診斷和治療指南》[7],且均為自發(fā)性心肌梗死;②患者及其家屬對(duì)本研究均知情同意,并簽署了知情同意書(shū)。排除標(biāo)準(zhǔn):①合并有惡性腫瘤、急慢性感染性疾病、血液系統(tǒng)等疾病者;②既往患有心臟瓣膜病、心肌炎、心肌病等心臟疾病者;③合并有肝、腎、肺、腦等重要臟器功能障礙者;④合并有精神疾病無(wú)法配合研究者。另選取同期在我院體檢顯示心功能正常的志愿者120例作為非STEMI組。兩組研究對(duì)象的一般資料比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P > 0.05),具有可比性。見(jiàn)表1。本研究已獲得了我院醫(yī)學(xué)倫理委員會(huì)批準(zhǔn)。

    1.2方法

    ①采用實(shí)時(shí)熒光定量PCR法檢測(cè)血清中miR-1-3p的相對(duì)表達(dá)量,抽取所有研究對(duì)象的空腹靜脈血5 mL,3000 r/min的速度離心15 min,離心半徑10 cm,血清,采用Trizol試劑盒(上海碧云天生物技術(shù)有限公司,生產(chǎn)批號(hào):20161003)提取血清中的總RNA,在A260/A280測(cè)定RNA濃度及純度合格后,采用逆轉(zhuǎn)錄試劑盒(大連寶生物工程有限公司,生產(chǎn)批號(hào):20160826)進(jìn)行逆轉(zhuǎn)錄,提取cDNA,以cDNA為模板對(duì)miR-1-3p進(jìn)行實(shí)時(shí)熒光定量PCR檢測(cè)。引物序列均由生工生物工程(上海)股份有限公司合成,內(nèi)參U6的上游引物:5′-C-TCGCTTCGGCAGCACA-3′,下游引物:5′-AACGCTT-CACGAATTTGCGT-3′;miR-1-3p上游引物:5′-CA-GTGCGTGTCGTGGAGT-3′,下游引物:5′-GGCCTGG-AATGTAAAGAAGT-3′。反應(yīng)條件:95℃,10 min;95℃,10 s;60℃,1 min,共40個(gè)循環(huán)。采用2-△△Ct法計(jì)算血清中miR-1-3p的相對(duì)表達(dá)量。②采用酶標(biāo)儀(XMark,美國(guó)Bio-Rad公司)及其配套試劑以酶聯(lián)免疫吸附法檢測(cè)血清H-FABP、N端腦鈉肽前體(NT-proBNP)的水平。③采用全自動(dòng)生化分析儀(日立,7600)檢測(cè)總膽固醇(TC)、低密度脂蛋白膽固醇(LDL-C)、三酰甘油(TG)的水平。④采用彩色超聲診斷儀(飛利浦IE33)測(cè)量左室射血分?jǐn)?shù)(LVEF)、左室舒張末期內(nèi)徑(LVEDD)。

    1.3 觀(guān)察指標(biāo)

    比較STEMI組和非STEMI組血清miR-1-3p、H-FABP、NT-proBNP、LVEF、LVEDD、TC、LDL-C、TG水平;分析STEMI患者血清miR-1-3p、H-FABP與脂代謝指標(biāo)、心功能指標(biāo)的相關(guān)性,及對(duì)STEMI的診斷價(jià)值。

    1.4 統(tǒng)計(jì)學(xué)方法

    采用SPSS 19.0對(duì)所得數(shù)據(jù)進(jìn)行統(tǒng)計(jì)學(xué)分析,計(jì)量資料均符合正態(tài)分布,采用均數(shù)±標(biāo)準(zhǔn)差(x±s)表示,組間比較采用t檢驗(yàn)。計(jì)數(shù)資料采用百分率表示,采用χ2檢驗(yàn)。受試者操作特征曲線(xiàn)(ROC)分析血清miR-1-3p、H-FABP及聯(lián)合檢測(cè)STEMI的診斷價(jià)值。采用Pearson進(jìn)行相關(guān)性分析。以P < 0.05為差異有統(tǒng)計(jì)學(xué)意義。

    2 結(jié)果

    2.1 兩組血清miR-1-3p、H-FABP水平比較

    STEMI組的血清miR-1-3p相對(duì)表達(dá)量低于非STEMI組,血清H-FABP水平高于非STEMI組,差異均有統(tǒng)計(jì)學(xué)意義(均P < 0.05)。見(jiàn)表2。

    2.2 兩組心功能指標(biāo)比較

    STEMI組的LVEF低于非STEMI組,血清NT-proBNP水平及LVEDD高于非STEMI組,差異均有統(tǒng)計(jì)學(xué)意義(均P < 0.05)。見(jiàn)表3。

    2.3兩組血脂指標(biāo)比較

    兩組血清TG比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P > 0.05),STEMI組血清TC、LDL-C水平高于非STEMI組,差異均有統(tǒng)計(jì)學(xué)意義(均P < 0.05)。見(jiàn)表4。

    2.4 STEMI患者血清miR-1-3p、H-FABP與脂代謝指標(biāo)、心功能指標(biāo)的相關(guān)性分析

    STEMI組血清miR-1-3p與TC、LDL-C、NT-proBNP、LVEDD、H-FABP均呈負(fù)相關(guān),與LVEF呈正相關(guān)(P < 0.05),血清H-FABP與TC、LDL-C、NT-proBNP、LVEDD均呈正相關(guān),與LVEF、miR-1-3p呈負(fù)相關(guān)(P < 0.05),二者與TG均無(wú)明顯的相關(guān)性(P > 0.05)。見(jiàn)表5。

    [4]? Shang A,Yang M,Shen F,et al. MiR-1-3p Suppresses the Proliferation,Invasion and Migration of Bladder Cancer Cells by Up-Regulating SFRP1 Expression [J]. Cell Physiol Biochem,2017,41(3):1179-1188.

    [5]? Li M,Chen X,Chen L,et al. MiR-1-3p that correlates with left ventricular function of HCM can serve as a potential target and differentiate HCM from DCM [J]. J Transl Med,2018,16(1):161.

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    [8]? 陳偉偉,高潤(rùn)霖,劉力生,等.《中國(guó)心血管病報(bào)告2017》概要[J].中國(guó)循環(huán)雜志,2018,33(1):1-8.

    [9]? Li J,Li X,Wang Q,et al. ST-segment elevation myocardial infarction in China from 2001 to 2011(the China PEACE-Retrospective Acute Myocardial Infarction Study):a retrospective analysis of hospital data [J]. Lancet,2015, 385(9966):441-451.

    [10]? 沈衛(wèi)峰,張奇,張瑞巖.2015年急性ST段抬高型心肌梗死診斷和治療指南解析[J].國(guó)際心血管病雜志,2015,42(4):217-219.

    [11]? 鄧麗,劉宏宇.循環(huán)miRNA作為心肌損傷標(biāo)志物的研究進(jìn)展[J].中華胸心血管外科雜志,2015,31(8):509-512.

    [12]? Sygitowicz G,Tomaniak M,B?覥aszczyk O,et al. Circulating microribonucleic acids miR-1,miR-21 and miR-208a in patients with symptomatic heart failure: Preliminary results [J]. Arch Cardiovasc Dis,2015,108(12):634-642.

    [13]? 羅水蓮,陳宇航,石毓君,等.microRNA-1抑制心肌特異性Dicer基因缺失小鼠心臟病理性重構(gòu)[J].第三軍醫(yī)大學(xué)學(xué)報(bào),2017,39(14):1469-1475.

    [14]? Yuan W,Tang C,Zhu W,et al. CDK6 mediates the effect of attenuation of miR-1 on provoking cardiomyocyte hypertrophy [J]. Mol Cell Biochem,2016,412(1/2):289-296.

    [15]? Xiong D,Heyman NS,Airey J,et al. Cardiac-specific,inducible ClC-3 gene deletion eliminates native volume-sensitive chloride channels and produces myocardial hypertrophy in adult mice [J]. J Mol Cell Cardiol,2010,48(1):211-219.

    [16]? Ye XD,He Y,Wang S,et al. Heart-type fatty acid binding protein(H-FABP)as a biomarker for acute myocardial injury and long-term post-ischemic prognosis [J]. Acta Pharmacol Sin,2018,39(7):1155-1163.

    [17]? 黃贊鴻,張惜鈴,林英奎,等.心型脂肪酸結(jié)合蛋白在急性心肌梗死早期診斷中的應(yīng)用[J].現(xiàn)代醫(yī)院,2017,17(10):1545-1548.

    [18]? 韓娟萍,張衛(wèi)澤,林麗霞,等.前列地爾對(duì)急性ST段抬高型心肌梗死PCI術(shù)后心肌缺血再灌注損傷的保護(hù)作用[J].疑難病雜志,2019,18(7):657-660.

    [19]? Liou K,Ho S,Ooi SY. Heart-type fatty acid binding protein in early diagnosis of myocardial infarction in the era of high-sensitivity troponin:a systematic review and meta-analysis [J]. Ann Clin Biochem,2015,52(Pt 3):370-381.

    [20]? 許佳昕,呂偉.急性ST段抬高型心肌梗死患者血清miR-1-3p、H-FABP檢測(cè)水平及與冠狀動(dòng)脈病變程度的關(guān)系[J].臨床急診雜志,2018,19(12):816-820.

    [21]? 李曉鵑,胡鵬,余強(qiáng),等.PCI術(shù)聯(lián)合依達(dá)拉奉治療ST段抬高型急性心肌梗死的療效及其機(jī)制研究[J].疑難病雜志,2018,17(8):757-761.

    [22]? 楊莉,柴國(guó)祥.急性心肌梗死患者血清IMA、miR-1、H-FABP水平變化及其診斷價(jià)值分析[J].山東醫(yī)藥,2019, 59(8):64-66.

    (收稿日期:2019-12-13? 本文編輯:顧家毓)

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