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CRP、TNF—α和血脂在冠心病不穩(wěn)定型心絞痛患者中的表達(dá)

2017-11-03 02:32王紅艷張艷霞
中國現(xiàn)代醫(yī)生 2017年27期
關(guān)鍵詞:不穩(wěn)定型心絞痛血脂

王紅艷  張艷霞

[摘要] 目的 研究冠心病不穩(wěn)定型心絞痛患者血清中CRP、TNF-α和血脂的表達(dá)水平,探討CRP、TNF-α、血脂三者與冠心病不穩(wěn)定型心絞痛之間的關(guān)系。 方法 收集2015年8月~2016年9月本院收治的46例不穩(wěn)定型心絞痛患者和40例穩(wěn)定型心絞痛患者的臨床資料進(jìn)行分析;并分別測定兩組患者和健康對照人群血清中CRP、TNF-α和血脂的表達(dá)水平。 結(jié)果 ELISA實驗結(jié)果表明,相比對照組人群,不穩(wěn)定型心絞痛患者血清中CRP和TNF-α表達(dá)水平明顯增加,LDL-C和TG含量也有所增加,與對照組比較,差異均有統(tǒng)計學(xué)意義(P<0.05);穩(wěn)定型心絞痛患者血清中CRP、LDL-C和TG含量有所增加,且差異具有統(tǒng)計學(xué)意義(P<0.05),而TNF-α、HDL-C和TC水平與健康對照人群比較,差異無統(tǒng)計學(xué)意義(P>0.05)。 結(jié)論 CRP、TNF-α和血脂可能與冠心病不穩(wěn)定型心絞痛的發(fā)生發(fā)展密切相關(guān),檢測冠心病不穩(wěn)定型心絞痛患者血清中CRP、TNF-α和血脂含量,對了解患者體內(nèi)免疫狀態(tài)、臨床診斷和預(yù)后有重要意義。

[關(guān)鍵詞] 不穩(wěn)定型心絞痛;CRP;TNF-α;血脂

[中圖分類號] R541.4 [文獻(xiàn)標(biāo)識碼] B [文章編號] 1673-9701(2017)27-0082-03

Expression of CRP, TNF-α and blood lipid in the patients with coronary heart disease complicated with unstable angina

WANG Hongyan ZHANG Yanxia

Department of No.1 Cardiology, Jiyuan Peoples Hospital in Henan Province, Jiyuan 459000, China

[Abstract] Objective To study the expression levels of serum CRP, TNF-α and blood lipids in the patients with coronary heart disease complicated with unstable angina, and to investigate the relationship between the three factors of CRP, TNF-α and blood lipid and coronary heart disease complicated with unstable angina. Methods The clinical data of 46 patients with unstable angina and 40 patients with stable angina who were admitted to our hospital from August 2015 to September 2016 were collected, and an overall analysis was made; the expression levels of serum CRP, TNF-α and blood lipids were measured in the patients with two types of diseases and healthy controls. Results The results of ELISA showed that the expression levels of serum CRP and TNF-α in the patients with unstable angina pectoris were significantly increased compared with the control group, and the LDL-C and TG levels were also increased. Compared with the control group, there were significant differences(P<0.05); the levels of serum CRP, LDL-C and TG in the patients with stable angina were increased, and the difference was statistically significant(P<0.05). However, TNF-α, HDL-C and TC levels did not change significantly compared with those in the healthy controls, and the difference was not statistically significant(P>0.05). Conclusion CRP, TNF-α and blood lipids may be closely related to the occurrence and development of coronary heart disease complicated with unstable angina. Detection of serum CRP, TNF-α and blood lipids levels in the patients with coronary heart disease complicated with unstable angina is of great significance to understand the immune status, clinical diagnosis and prognosis of the patients.endprint

[Key words] Unstable angina; CRP; TNF-α; Blood lipids

冠心病不穩(wěn)定型心絞痛(unstable angina,UA)是介于穩(wěn)定型心絞痛與急性心肌梗死及心臟猝死之間的一種臨床狀態(tài),其發(fā)病原因與年齡增加、高血脂、糖尿病和腎功能障礙等相關(guān)疾病、動脈粥樣硬化和血管壁斑塊破裂等密切相關(guān)[1]。研究表明,機(jī)體炎癥反應(yīng)和相關(guān)細(xì)胞因子是引起粥樣血栓的主要因素,而單核巨噬細(xì)胞又在此過程中起關(guān)鍵作用,由其產(chǎn)生并分泌的腫瘤壞死因子-α(TNF-α)及其誘導(dǎo)肝臟產(chǎn)生的急性反應(yīng)蛋白C-反應(yīng)蛋白(CRP)是炎癥和免疫反應(yīng)的重要介質(zhì)。這些炎癥因子和血脂在冠狀動脈斑塊的發(fā)生發(fā)展及不穩(wěn)定性斑塊破裂而激發(fā)的血栓形成過程中可能起重要作用[2]。本文主要檢測了穩(wěn)定型心絞痛患者和不穩(wěn)定型心絞痛患者血清中CRP、TNF-α和血脂(LDL-C、HDL-C、TC和TG)的水平,與正常人群進(jìn)行比較,以探討這三者在不穩(wěn)定型心絞痛患者血清中的變化以及在不穩(wěn)定型心絞痛發(fā)病機(jī)制中的作用,以為臨床上開發(fā)UA新的治療方法提供實驗依據(jù),并為UA的臨床診斷和病情判斷提供指導(dǎo)意義。

1 資料與方法

1.1 一般資料

選取2015年8月~2016年9月本院收治的冠心病患者86例,冠心病診斷符合以下條件之一:有急性心肌梗死病史;有一支及以上冠狀動脈狹窄超過50%;發(fā)病時出現(xiàn)短暫性缺血性ST-T改變。86例患者中包括40例穩(wěn)定型心絞痛患者和46例不穩(wěn)定型心絞痛患者,根據(jù)年齡選取相應(yīng)的健康對照組25例,均為常規(guī)體檢中無任何異常者,年齡55~65歲,各組男女性別比均具有可比性。冠心病不穩(wěn)定型心絞痛患者為UA組,健康受試者為正常對照組。三組的臨床基本情況比較結(jié)果如下:UA組、穩(wěn)定型心絞痛組和正常對照組年齡、性別、吸煙比例、高血壓比例和糖尿病比例比較,差異均無統(tǒng)計學(xué)意義(P>0.05),此外,三組間血糖比較,差異無統(tǒng)計學(xué)意義(P>0.05)。見表1。

1.2 診斷與納入標(biāo)準(zhǔn)

符合1979年WHO提出的《缺血性心臟病的命名及診斷標(biāo)準(zhǔn)》,并結(jié)合冠狀動脈CT或冠狀動脈造影(coronary arteriography,CAG)(冠狀動脈主要血管直徑狹窄程度≥50%),或既往有心肌梗死病史為冠心病診斷標(biāo)準(zhǔn)。符合2001年中華醫(yī)學(xué)會心血管病學(xué)分會和中華心血管病雜志編輯委員會制定的《不穩(wěn)定型心絞痛診斷和治療建議》中不穩(wěn)定型心絞痛診斷標(biāo)準(zhǔn)[3]。該研究方案由本院倫理委員會批準(zhǔn),并獲得所有受試者知情同意。

1.3 方法

1.3.1 標(biāo)本采集 所有試驗對象均未使用降脂、抗凝、抗菌藥物,于清晨空腹抽取外周靜脈血6 mL,樣品于4℃冰箱靜置1 h后,3000 rpm離心10 min,取上清液轉(zhuǎn)移至新的離心管中,即為對應(yīng)的新鮮血清,儲存于-80℃?zhèn)溆谩?/p>

1.3.2 主要儀器與試劑 酶聯(lián)免疫檢測儀為Thermo Multiskan Ascent,全自動生化分析儀為深圳邁瑞B(yǎng)S-200,CRP試劑盒和TNF-α試劑盒均購自上海吉泰依科賽生物科技有限公司。

1.3.3 ELISA法測定血清中CRP和TNF-α的含量 取出待測樣品于試劑盒,平衡至室溫。取出試劑盒中的標(biāo)準(zhǔn)品,根據(jù)說明書要求加入對應(yīng)體積的試劑稀釋液或雙蒸水;靜置10~20 min,輕柔搖晃標(biāo)準(zhǔn)品,使其充分溶解。嚴(yán)格按照CRP和TNF-α試劑盒說明書進(jìn)行操作,采用酶聯(lián)免疫吸附試驗測定血清中CRP和TNF-α的含量。

1.3.4 血脂含量的測定 取血液樣品,全自動生化分析儀測定血脂水平,包括總膽固醇(TC)、甘油三酯(TG)、低密度脂蛋白膽固醇(LDL-C)和高密度脂蛋白膽固醇(HDL-C)。所有試驗均設(shè)三個復(fù)孔。

1.4 統(tǒng)計學(xué)分析

采用SPSS 12.0統(tǒng)計學(xué)軟件進(jìn)行統(tǒng)計分析。計量資料采用(x±s)表示,兩組組間比較采用t檢驗;多組間比較采用方差分析;計數(shù)資料用百分率表示,采用χ2檢驗,P<0.05表示差異有統(tǒng)計學(xué)意義。

2 結(jié)果

ELISA結(jié)果顯示,不穩(wěn)定型心絞痛患者血清中CRP的含量高于穩(wěn)定型心絞痛患者和健康對照人群,且差異有統(tǒng)計學(xué)意義(P<0.01)。穩(wěn)定型心絞痛患者中CRP水平也高于健康對照人群,差異具有統(tǒng)計學(xué)意義(P<0.05)。不穩(wěn)定型心絞痛患者血清中TNF-α的含量高于穩(wěn)定型心絞痛患者和健康對照人群,差異有統(tǒng)計學(xué)意義(P<0.01)。穩(wěn)定型心絞痛患者血清中TNF-α與健康對照人群相比,差異無統(tǒng)計學(xué)意義(P>0.05)。冠心病不穩(wěn)定型心絞痛患者與穩(wěn)定型心絞痛患者血清中LDL-C和TG含量均增加,與對照組比較,差異有統(tǒng)計學(xué)意義(P<0.05),而UA組患者和穩(wěn)定型心絞痛患者血清內(nèi)HDL-C和TC水平與健康對照人群比較,差異無統(tǒng)計學(xué)意義(P>0.05)。

3 討論

根據(jù)修訂的心肌梗死(MI)定義,患有缺血、但其中生物標(biāo)志物僅有輕微升高和降低的患者,現(xiàn)被認(rèn)為具有真正的心肌損傷[4]。從2000年至今,不穩(wěn)定型心絞痛通過劃分肌鈣蛋白陽性和肌鈣蛋白陰性來劃分,因此,1989年對不穩(wěn)定型心絞痛的臨床定義仍是最合適的描述[5]。心絞痛被認(rèn)為在心肌的冠狀血管上血流被剝奪導(dǎo)致的一種胸部不適情況[6],穩(wěn)定型心絞痛主要是心外膜冠狀動脈內(nèi)腔減少引起冠狀動脈粥樣硬化[7],而不穩(wěn)定型心絞痛是一種心臟沒有得到足夠血流量和氧氣的狀態(tài)[8],可能導(dǎo)致心臟病發(fā)作。

CRP是一種由單核細(xì)胞合成的急性期反應(yīng)蛋白,在IL-6的誘導(dǎo)下啟動凝血過程[9]。CRP通過結(jié)合磷酸膽堿發(fā)揮生物學(xué)活性,在即將死亡或者已經(jīng)死亡的細(xì)胞表面刺激免疫系統(tǒng)[10,11]。TNF-α是一種具有多種生物活性的細(xì)胞因子,主要參與抗感染、機(jī)體免疫調(diào)節(jié)以及增強(qiáng)單核細(xì)胞的活性,在機(jī)體免疫防御系統(tǒng)中起重要作用[12]。TNF-α主要由巨噬細(xì)胞分泌,并以自分泌方式促進(jìn)自身的合成,集中合成在病變部位,各類感染和外界刺激均能引起TNF-α的表達(dá)增加。生理狀態(tài)或激活狀態(tài)下的TNF-α均能抑制血管平滑肌細(xì)胞的膠原基因表達(dá),使斑塊不穩(wěn)定。TNF-α可促進(jìn)原癌基因的表達(dá),產(chǎn)生血小板生長因子,使血凝-抗凝系統(tǒng)失衡,促進(jìn)血栓的形成,引起不穩(wěn)定型心絞痛的發(fā)生[13]。血清中總膽固醇(TC)和低密度脂蛋白膽固醇(LDL-C)是冠狀動脈疾病的臨床表現(xiàn)[14],而冠狀動脈粥樣硬化和血栓形成可導(dǎo)致冠心病的形成。研究表明,血脂在不穩(wěn)定型心絞痛的發(fā)生發(fā)展中可能有一定作用。endprint

本研究結(jié)果表明,不穩(wěn)定型心絞痛患者血清中CRP、TNF-α、低密度脂蛋白膽固醇(LDL-C)和甘油三酯(TG)的含量均顯著高于穩(wěn)定型心絞痛患者和正常對照人群;相比正常人群和穩(wěn)定型心絞痛患者,不穩(wěn)定型心絞痛患者血脂表達(dá)水平明顯降低。相比正常對照人群,穩(wěn)定型心絞痛患者血清中CRP、TG和LDL-C水平明顯升高,而TNF-α、TC和HDL-C水平無顯著差異。此結(jié)果提示CRP、TNF-α、TG和LDL-C在動脈粥樣硬化的發(fā)生發(fā)展中具有重要作用,也可能是不穩(wěn)定型心絞痛的重要發(fā)病機(jī)制之一[15]。關(guān)于CRP、TNF-α和血脂在冠心病不穩(wěn)定型心絞痛的發(fā)病中具體分子機(jī)制及如何參與調(diào)控UA的發(fā)展,還有待進(jìn)一步研究。

[參考文獻(xiàn)]

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[2] He W,Wang Z,Cai J,et al. Concentration of plasma vascular endothelial growth factor and related factors in patients with unstable angina pectoris[J]. Zhonghua Xin Xue Guan Bing Za Zhi,2015,43(12):1057-1060.

[3] 中華醫(yī)學(xué)會心血管病學(xué)分會,中華心血管病雜志編輯委員會. 不穩(wěn)定型心絞痛診斷和治療建議[J]. 中國循環(huán)雜志,2001,16(3):227-229.

[4] Xia Y,Xia Y,Xu K,et al. Predictive value of the novel risk score BETTER(BiomarkErs and computed tomogra-phy score on risk stratification) for patients with unstable angina[J]. Herz,2015,40(Suppl):143-150.

[5] Braunwald E,Morrow DA. Unstable angina:Is it time for a requiem?[J]. Circulation,2013,127(24):2452-2457.

[6] Yang J,Liu C,Zhang L,et al. Intensive Atorvastatin Therapy Attenuates the Inflammatory Responses in Monocytes of Patients with Unstable Angina Undergoing Percutaneous Coronary Intervention via Peroxisome Pro-liferator-Activated Receptor gamma Activation[J]. Inflammation,2015,38(4):1415-1423.

[7] Hao J,Du H,Li W,et al. Effects of atorvastatin combined with trimetazidine on myocardial injury and inflammatory mediator in unstable angina patients during perioperative of percutaneous coronary intervention[J]. Eur Rev Med Pharmacol Sci,2015,19(23):4642-4646.

[8] Deckers JW. Classification of myocardial infarction and unstable angina:A re-assessment[J]. Int J Cardiol,2013, 167(6):2387-2390.

[9] Huang D,Yang CZ,Yao L,et al. Activation and overexpression of PARP-1 in circulating mononuclear cells promote TNF-alpha and IL-6 expression in patients with unstable angina[J]. Arch Med Res,2008,39(8):775-784.

[10] Wang LX,Lu SZ,Zhang WJ,et al. Comparision of high sensitivity C-reactive protein and matrix metalloproteinase 9 in patients with unstable angina between with and without significant coronary artery plaques[J]. Chin Med J(Engl), 2011,124(11):1657-1661.endprint

[11] Su Q,Li L,Liu Y,et al. Effect of intensive atorvastatin therapy on periprocedural PDCD4 expression in CD4+T lymphocytes of patients with unstable angina undergoing percutaneous coronary intervention[J]. Cardiology,2014, 127(3):169-175.

[12] Shevchenko AV,Golovanova OV,Konenkov VI,et al. Analysis of polymorphism of three positions of promoter region of TNF-gene in patients with ischemic heart disease, unstable angina and myocardial infarction[J]. Kardiologiia,2010,50(2):9-14.

[13] Al-Karkhi IH,Ibrahim AE,Yaseen AK. Levels of insulin, IL-6 and CRP in patients with unstable angina[J]. Adv Clin Exp Med,2013,22(5):655-658.

[14] Cui F,Zhang Y,Wei Q,et al. A Novel Medical Treatment for Lipid Control in Patients with Unstable Angina Pectoris and Statin-Induced Liver Dysfunction[J]. Acta Cardiol Sin,2015,31(1):66-71.

[15] Gencer B,Auer R,de Rekeneire N,et al.Association between resistin levels and cardiovascular disease events in older adults:The health,aging and body composition study[J].Atherosclerosis,2016,245(10):181-186.

(收稿日期 :2017-07-07)endprint

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