血清hsCRP水平与糖尿病冠状动脉弥漫病变关系探讨

中图分类号:R587.1 文献标 识码:A 文章编号:1009_816X(2010)03_0174_03

Increased Serum High Sensitivity C_reactive Protein Level is Associated with Dif fuse Coronary Artery Lesions in Patients with Type 2 Diabetes.WU Mei_cui, LU Lin,LIN Zu_jin. Department of Cardiology, Taizhou Central Hospi tal, Zhejiang 318000, China

[Abstract] Objective The aim of this study was to determine the prognostic valueof high sensitivity C_reactive protein (hsCRP) for diffuse coronary artery lesi ons in patients with type 2 diabetes.MethodsA total of 296 patients with coron ary artery disease(CAD) confirmed by angiography were divided into 5 groups base d upon coronary angiographic findings and with or without diabetes: 92 patientshad focal coronary artery lesions without diabetic(group I), 78 patients had dif fuse coronary artery lesions without diabetes(group II), 30 patients had diabete s but not CAD (group III), 32 diabetic patients with focal coronary artery lesio ns (group IV); and 64 diabetic patients with diffuse coronary artery lesions (gr oup V) , Serum levels of hsCRP, TNF_α and IL_6 were measured in all subjects.Results Serum hsCRP level was significantly higher(p

[Key words] C_reactive protein; Diabetes mellitus; Diffuse coronary artery lesions

糖尿病是冠心病的主要危险因素,合并糖尿病的冠心病患者冠状动脉病变以多支弥漫病变多 见且预后较差[1,2]。近年来研究认为,糖尿病和动脉硬化均为低度炎症性疾病[3]。冠心病或糖尿病患者血清炎症标志物C反应蛋白水平均明显高于健康人,并认为 hsCR P是冠状动脉硬化的发生、发展及预后的强预测因子之一,hsCRP水平升高者发生心血管事件 风险明显增高[4]。糖尿病患者CRP升高对其血管并发症也有一定预示作用[5 ]。本文探讨炎症因子(hsCRP、IL_6、TNF_α)与糖尿病冠状动脉弥漫病变的关系。

1 资料和方法

1.1 一般资料:选择2006年1月至2008年12月在我院心内科住院经冠脉造影患者296例,根 据冠脉病变和有无糖尿病将患者分成五组:单纯冠心病冠脉局 灶病变组(I组)92例,男67例,女25例,年龄(64.4±10.6)岁;单纯冠心病冠脉弥漫病 变组(II组)78例,男54例,女24例,年龄(67.2±9.2)岁;单纯糖尿病组(III 组)30例,男17例,女13例,年龄(61.2±10.0)岁,经冠状动脉造影冠状动脉无狭窄病变 ;冠心病合并2型糖尿病冠脉局灶病变组(IV组)32例,男18例,女14例,年龄(66.4±10 .4)岁。冠心病合并2型糖尿病冠脉弥漫病变组(V组)64例,男43例,女21例,年龄( 66.7±10.0)岁。

冠心病诊断为至少有一支冠状动脉管腔直径50%狭窄病变;弥漫性冠状动脉病变的判断根 据1988年美国ACC/AHA冠脉形态分类标准,靶病变长度20mm为弥漫性长病变,或至少1/3血 管长度存在3处或3处以上50%的狭窄病变[6]。靶病变长度10mm为局灶病变。 糖尿病诊断根据美国糖尿病协会(ADA)提出的2型糖尿病诊断标准,其中包括以往确诊为糖尿 病目前仍服用降糖药或应用胰岛素控制血糖者。排除明确的急慢性感染,恶性肿瘤,自身免 疫性疾病,严重肝肾功能不全及急性心肌梗死患者。

1.2 方法:采集禁食8小时以上空腹血5ml。以3000转/分离心10分钟,分离血清并于-70℃ 冰箱冻存待测。hsCRP测定采用高敏酶联免疫测定(ELISA)法测定:试剂盒购自美国Biocheck实验室(参考 范围为0.62～119.3mg/L);血清IL_6、TNF_α测定采用ELISA法测定,试剂盒分别为美国R &D公司的人类TNF_α/TNFSF1A Quantikine ELISA试剂盒和美国R&D公司Quantikine HS IL_6 试剂盒。

1.3 统计学方法:应用SPSS13.0统计软件包,计量资料采用均数±标准差,五组间采用 方差分析,其中多组两两间采用LSD法检验结果;由于甘油三酯(TG),脂蛋白a(LPa),h sCRP以及TNF_α为非正态分布,予行对数转换后进行上述检验。计数资料采用卡方检验, 因素之间关系采用spearman's相关分析。P

2 结果

2.1 各组临床资料比较:见表1。各组在高血脂、高血压、吸烟等方面无明显差别。在单 纯 冠心病和冠心病合并糖尿病四组中年龄均大于单纯糖尿病患者,其中冠心病局灶病变和单纯 糖尿病之间比较无统计学意义,余均P

2.2 血清hs_CRP水平:在冠心病合并糖尿病冠状动脉弥漫病变组(14.65±8.74mg/L) 明显高于其它四组(均P

血清TNF_α、IL_6水平在冠心病合并糖尿病冠状动脉局灶病变(IV组)和弥漫病变组(V组) 水平高于单纯糖尿病(III组)和非糖尿病冠心病组(I、II组),血清TNF_α水平IV组最高 较II组、III组高有统计学意义(77.7±41.65 vs.64.10±49.17、59.38±41.54pg /ml,P

3 讨论

共同土壤学说提出糖尿病、冠心病均是一种慢性炎症性疾病,糖尿病即冠心病的等危症 [7]。研究发现CRP是炎症反应的重要临床指标[8],主要由肝脏产生并分 泌,其表达主要受白细胞介素6(IL_6)的调控,人体脂肪细胞和动脉粥样斑块中的巨噬细 胞也能合成CRP[9],CRP与动脉粥样硬化斑块的形成、发展及斑块的不稳定有关[10],是冠心病、糖尿病心血管系统以及其他脏器并发症的独立预测因子[11～ 13]。

本文发现在糖尿病合并冠状动脉的两组hsCRP、TNF_α、IL_6水平明显高于单纯糖尿病组和 单纯冠心病两组,其中血清hsCRP水平在糖尿病冠脉弥漫病变组又明显高于糖尿病冠状动脉 局灶病变组(均P

以往研究[14]发现,在糖尿病、冠心病时TNF_α、IL_1、IL_6等炎性因子 分泌增加,促使肝脏分泌CRP增加。许多研究证实在冠心病患者中血清CRP水平明显高于正常 人群,尸体解剖也发现在人类早期冠状动脉粥样斑块中就存在大量CRP的沉积[15] ,说明hsCRP升高与糖尿病动脉硬化的发生发展可能互为因果。有报道显示,动脉粥样硬化 患者普遍存在循环中IL_6水平的增高,并证明IL_6在动脉粥样硬化斑块中大量存在,特别是 在巨噬细胞浸润区[16]。因此本文认为糖尿病患者hsCRP水平升高不仅是动脉硬 化并发症发生的主要危险因素,也是发生冠状动脉弥漫病变的主要预测指标。早期监测糖尿 病患者的hsCRP水平可能有助于防治糖尿病冠状动脉弥漫病变的发生发展。

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