第10章 心血管疾病的生物化学检验课件

十章 心血管系统疾病 的生物化学检验 （双语） 1 背景资料 2006年中国城市居民前十位死因 美国前十位死 因 1. 恶性肿瘤27.3% 心脏病 27.2% 2. 脑血管病17.7% 恶性肿瘤 23.1% 3. 心脏病17.1% 脑血管病 6.3% 4. 呼吸系病13.1% 慢性呼吸道疾 病 5. 损伤及中毒6.1% 意外事件 6. 内分泌营养和代谢疾病3.3% 糖尿病 7. 消化系病2.9% 阿兹海默症 8. 泌尿生殖系病1.4% 流行性感冒和 肺炎 9. 神经系病0.9% 肾脏疾病 10. 精神障碍0.7% 败血病 前十位死因占中国死亡总数的90.4， 美国78 。 2 主要内容 第一节 概述 第二节 心血管疾病主要生化检测指标 第三节心血管疾病主要生化检测指标的临 床应用 3 第一节 概述 一、心脏的解剖和生理 心肌富含的蛋白与酶？有何临床意义？ 肌钙蛋白 肌红蛋白 CK LD 4 心肌血液供应来自主动脉根部发出的左右冠状 动脉，冠状动脉主干行走于心脏表面，沿途发出分 支，在心肌和心内膜下层形成丰富的毛细血管网， 毛细血管与心肌比例高达1:1。 5 备注： 内膜 内皮细 胞 基膜 内弹性 膜 中膜 外弹性 膜 平滑肌 外膜 内腔 内皮细 胞 基膜 6 Heart Disease Heart disease is a general term that refers to a variety of acute and chronic medical conditions that affect one or more of the components of the heart. The heart is a muscular, fist-sized organ that is located in the left side of the chest cavity胸腔. It continuously pumps blood, beating as many as 100,000 times a day. The blood that the heart moves carries oxygen and nutrients营养 素 throughout the body and transports carbon dioxide二氧化碳 and other wastes to the lungs, kidneys, and liver for removal. 7 The heart ensures its own oxygen supply through a set of coronary arteries冠 状动脉 and veins. The heart is also an endocrine内分泌的 organ that produces the hormones atrial natriuretic hormone (ANP) 心房利钠肽,心钠素 and B-type natriuretic peptide (BNP), which coordinate协调 heart function with blood vessels and the kidneys. 8 Diseases affecting the heart may be structural or functional. Anything that damages the heart or decreases the hearts supply of oxygen, makes it less efficient, reduces its ability to fill and pump, will disrupt the coordinated relationship between the heart, kidneys, and blood vessels and will harm not only the heart but the rest of the body as well. 9 Heart diseases may be due to: Atherosclerosis动脉粥样硬化Common disorder of the arteries in which deposits沉着 物consisting mostly of cholesterol胆固醇and lipids form on the inner arterial wall. As a result, the vessels become nonelastic无弹性的 and narrowed, leading to decreased blood flow. One of the most important examples is coronary artery disease冠心病. 10 Autoimmune conditions Congenital abnormalities先天性异常 Hypertension高血压 Diabetes糖尿病 Thyroid dysfunction (under and overactive)甲状腺功能异常 Diet, especially when high in saturated fat饱和脂肪and cholesterol 11 Injury or trauma Smoking Alcohol use Cocaine use可卡因 Anabolic steroid use促蛋白合成类固醇 Toxins, such as mercury水银, and sometimes chemotherapy drugs or HIV/AIDS drugs Bacterial infection Viral infection 12 二心血管疾病 （一） 动脉粥样硬化及冠心病 动脉粥样硬化(atherosclerosis, AS)：多 因素导致动脉壁增厚、变硬、弹性减弱和管腔 缩小；病变动脉壁内层形成很多黄色粥样的斑 块，局部出现脂质、复合糖类的积聚，易形成 血栓，纤维组织增生和钙质沉着，动脉的退化 和钙化。 根据侵犯部位不同分为脑动脉硬化、主动 脉硬化、冠状动脉硬化、肾动脉硬化或周围动 脉硬化等不同类型。 13 AS的病理机制 AS是多因素综合作用的复杂过程 。 内皮细胞损伤和单核-巨噬细胞浸润及平滑 肌细胞转移 脂质的作用 血液凝集系统的激活及血栓形成 14 15 正常和动脉粥样硬化动脉比较 16 毛细血管 奔涌的血 管 17 动脉粥样血栓的形成 18 动脉粥样硬化 视频动脉粥样硬 化形成过程 .flv 19 二、冠心病及其他心血管事件 冠状动脉性心脏病(coronary artery heart disease, CHD)简称冠心病：各种原因致冠状动 脉狭窄，供血不足而引起的心肌功能障碍和/或器 质性病变 。 coronary heart disease (CHD) coronary artery disease (CAD) 95%以上CHD由冠状动脉粥样硬化引起，故 常将CHD与冠状动脉粥样硬化性心脏病混用。 冠心病分为心绞痛和心肌梗死两种临床类型 。 20 21 （一）心绞痛 (angina) 冠状动脉绝对或相对供血不足，心肌急 剧而短暂的缺血（氧）所致的临床综合征。 稳定型心绞痛(stable angina pectoris, SAP) 劳累型，最常见 变异型心绞痛(variant angina pectoris,VAP) 休息或夜间熟睡后发生 不稳定型心绞痛(unstable angina pectoris,UAP ) 介于稳定型心绞痛与心肌梗死间22 (二)急性心肌梗死 (acute myocardial infarction, AMI) 某支冠状动脉闭塞，血液供应中断，其 供血区域心肌因持久性缺血而发生的局部坏死。 透壁性心肌梗死：梗死灶累及心室壁全层，又 称Q波心肌梗死或ST段抬高心肌梗死。 灶性心肌梗死：梗死灶较小并灶性分布。 心内膜下心肌梗死：梗死灶局限于心壁内1/2 ，小灶性但分布较广。 后两类AMI常无的典型心电图改变，统称 非Q波心肌梗死（NQMI），生化检验有助诊断。 23 （三）急性冠脉综合征 急性冠脉综合征(acute coronary syndrome，ACS) ：UAP和AMI统称。 UAP：血栓部分阻塞 AMI：血栓完全阻塞 冠状动脉粥样硬化斑块由稳定转为不稳定 ，继而破裂导致血栓形成。 24 心肌病：心肌肥厚，扩张，纤维化，心肌 小范围损伤。 心力衰竭（心功能不全）：泵血功能障碍 。 高血压：原发性，继发性 25 第二节 心血管疾病主要生化检测 指标 一 动脉粥样硬化及冠心病的危险 因素 (一) 危险因素 (risk factor) ： 与某种疾病发生、发展有关的体内、 行为和环境因素。 相对危险度(relative risk, RR)： 暴露于该危险因素者与未暴露或低于 危险水平者发病概率的比值。RR1才有意义， 越大则预测价值越高。 (二) 动脉粥样硬化及冠心病的危险因素 : 26 第二节 心血管疾病主要生化检测 指标 一 心血管疾病危险因素相关生化指标 （一）血清脂质 致AS脂蛋白表型(致AS脂蛋白谱) 高TC、LDL-C, 低HDL-C作为AS独立危险因素 早获公认。TC/HDL-C比值与冠心病危险度呈对数线 性关系， TC/HDL-C比值5冠心病风险显著增大。 新显现的AS脂质危险因素：高TG、高载脂蛋白 ClIIlII、Lp(a) 、 载脂蛋白B 。 常规测定： TG 、TC、LDL-C 、HDL-C 27 (二)超敏C反应蛋白(high sensitivity C- reaction protein, hs-CRP） CRP是多种致炎因素刺激肝细胞和血管内皮 细胞产生的急性时相反应蛋白。 Your liver produces C-reactive protein (CRP) in response to injury or infection. CRP is also produced by muscle cells within the coronary arteries. CRP is a general sign of inflammation, which plays a central role in atherosclerosis. 。 28 因AS为慢性炎症过程，只有检测到CRP轻度 升高的状态才有价值。因此建立高灵敏度(灵敏度 0.3 mg/L )的CRP检测方法，即hs-CRP的由来。 高敏C反应蛋白的测定多采用其特异性抗体的定量 免疫学方法，包括免疫浊度法、ELISA法、放射免 疫法等。 参考值：用于AS危险性评估时，hs-CRP 10mg/L ，则可能存在其他急性炎症，应在控制后重新测定 。 29 hs-CRP是AS炎症状态危险因子中目前唯 一实际应用者。研究证实其RR远远高于任何 脂质因素，hs-CRP和TC/HDL-C联合应用， RR高达5.2。 hs-CRP亦是AS病变活跃，斑块破裂，血 栓形成的标志。现推荐CHD患者常规监测hs- CRP，以预测AMI和冠脉性猝死等冠脉事件的 发生，hs-CRP升高者需积极干预。 作业：简述超敏CRP与CRP的异同？ 30 （三）新型炎症反应标志物 IL-6、E-选择素(E-selectin)和P-选择素 (P-selectin) 、可溶性细胞间粘附分子 l(sICAM-1)已被列为新显现的AS危险因素， 但仍主要在研究中应用。 脂蛋白相关磷脂酶A2 ( Lp-PLA2 ) 巨噬细胞和淋巴细胞产生，独立危险 因子 31 32 （四） 促血栓形成相关危险因子 (1)纤溶酶原激活剂抑制物1 (plasminogen activator inhibitor-1, PAI-1) 抑制激活纤溶酶原稳定血栓 (2)血浆纤维蛋白原(fibrinogen, Fg)即凝 血因子I (3)凝血因子VII 33 （五）同型半胱氨酸 Homocysteine HCY 过多HCY形成硫内酯，与LDL表面载 脂蛋白的游离氨基酸形成肽键，促进细胞 摄取LDL，加速胆固醇沉积。 冠心病独立因素 34 正常空腹血浆总Hcy水平为515mol/L 。研究表明：Hcy每升高5umol/L脑卒中风险 升高59%，缺血性心脏病风险升高32%； 代谢辅助因子如叶酸、维生素B6、B12缺 乏，均可导致高同型半胱氨酸血症的发生。中 国人的饮食习惯吃煮熟的食物(叶酸主要存在于 蔬菜、肉类、动物肝脏等)，食物在煮熟的过程 中90%以上的叶酸被破坏，导致中国人普遍的 叶酸缺乏。 35 36 几种冠心病检测方法（指标）比较 血管造影：可显示血管狭窄，有创性检查 ，不适于普查、预防、检测。 血脂：最常用，受脂代谢影响，特异性较 低 心肌梗死标志物：在心肌梗死时显著，预 防意义较低。 Hs-CRP：较常用，受感染影响较大。 Hcy：较常用，易纠正 Lp-PLA2 ：不常用，贵，有前景 37 分 类类 主 要 危 险险 因 素 主要独立 危险险因素 吸烟、糖尿病、高血压压、高LDL-C、低HDL- C、有成年前发发生AS家族史、年龄龄 潜在的危 险险因素 致AS饮饮食、超重/肥胖、缺乏体力活动动、遗遗 传传影响 新显现显现 的 危险险因素 新脂质质危险险因素：高TG，高sd-LDL，高 Lp(a)，高ApoB等 促血栓形成状态态：高血小板凝集性，高血浆浆 纤维纤维 蛋白原等 促炎症状态态：高敏C反应应蛋白(hs-CRP), 白介 素6(IL-6等 胰岛岛素抵抗/糖耐量异常 38 Risk Factors and Coronary Heart Disease American Heart Association : Extensive clinical and statistical studies have identified several factors that increase the risk of coronary heart disease and heart attack. Major risk factors are those that research has shown significantly increase the risk of heart and blood vessel (cardiovascular 心血管的) disease. Other factors are associated with increased risk of cardiovascular disease, but their significance and prevalence患病率,流行率 havent yet been precisely精确地 determined. Theyre called contributing risk factors. 39 The American Heart Association has identified several risk factors. Some of them can be modified缓和,减轻 treated or controlled, and some cant. The more risk factors you have, the greater your chance of developing coronary heart disease. Also, the greater the level of each risk factor, the greater the risk. For example, a person with a total cholesterol of 300 mg/dL (milligram per deciliter ) has a greater risk than someone with a total cholesterol of 245 mg/dL, even though everyone with a total cholesterol greater than 240 is considered high-risk. 40 What are the major risk factors that cant be changed? Increasing age Over 83 percent of people who die of coronary heart disease are 65 or older. Male sex (gender性别) Men have a greater risk of heart attack than women do, and they have attacks earlier in life. Even after menopause绝经(期), when womens death rate from heart disease increases, its not as great as mens. 41 年龄与性别 42 43 Heredity 遗传 (including Race种族) Children of parents with heart disease are more likely to develop it themselves. African Americans have more severe high blood pressure than Caucasians高加索人,白种人 and a higher risk of heart disease. Heart disease risk is also higher among Mexican Americans, American Indians, native Hawaiians and some Asian Americans. This is partly due to higher rates of obesity肥胖 and diabetes糖尿病. Just as you cant control your age, sex and race, you cant control your family history. Therefore, its even more important to treat and control any other risk factors you have. 44 What are the major risk factors you can modify, treat or control by changing your lifestyle or taking medicine? High blood cholesterol As blood cholesterol rises, so does risk of coronary heart disease. When other risk factors (such as high blood pressure and tobacco smoke) are present, this risk increases even more. A persons cholesterol level is also affected by age, sex, heredity and diet. 45 Tobacco smoke Smokers risk of developing coronary heart disease is 24 times that of nonsmokers. Cigarette smoking is a powerful independent risk factor for sudden cardiac death in patients with coronary heart disease; smokers have about twice the risk of nonsmokers. Cigarette smoking also acts with other risk factors to greatly increase the risk for coronary heart disease. Exposure to other peoples smoke increases the risk of heart disease even for nonsmokers. 46 High blood pressure High blood pressure increases the hearts workload, causing the heart to thicken变厚 and become stiffer僵硬. It also increases your risk of stroke中风, heart attack, kidney failure and congestive heart failure充血性心力衰竭. When high blood pressure exists with obesity, smoking, high blood cholesterol levels or diabetes, the risk of heart attack or stroke increases several times. 47 Physical inactivity An inactive lifestyle is a risk factor for coronary heart disease. Regular, moderate-to-vigorous physical activity helps prevent heart and blood vessel disease. The more vigorous the activity, the greater your benefits. However, even moderate-intensity中度强度 activities help if done regularly and long term. Physical activity can help control blood cholesterol, diabetes and obesity, as well as help lower blood pressure in some people. 48 Obesity and overweight People who have excess body fat especially if a lot of it is at the waist腰部 are more likely to develop heart disease and stroke even if they have no other risk factors. Excess weight increases the hearts work. It also raises blood pressure and blood cholesterol and triglyceride甘油三酯 levels, and lowers HDL (“good“) cholesterol levels. It can also make diabetes more likely to develop. Many obese 肥胖的 and overweight people may have difficulty losing weight. But by losing even as few as 10 pounds, you can lower your heart disease risk. 49 肥 胖 50 51 Diabetes Diabetes seriously increases your risk of developing cardiovascular disease. Even when glucose (blood sugar) levels are under control, diabetes increases the risk of heart disease and stroke, but the risks are even greater if blood sugar is not well controlled. About three-quarters of people with diabetes die of some form of heart or blood vessel disease. 52 What other factors contribute to heart disease risk? Individual response to stress may be a contributing factor. Some scientists have noted a relationship between coronary heart disease risk and stress in a persons life, their health behaviors and socioeconomic社会经济 的 status. These factors may affect established确定的risk factors. For example, people under stress may overeat, start smoking or smoke more than they otherwise would. 53 Drinking too much alcohol can raise blood pressure, cause heart failure and lead to stroke. It can contribute to high triglycerides, cancer and other diseases, and produce irregular不齐的 heartbeats. It contributes to obesity, alcoholism酒精中毒, suicide and accidents. 54 Cardiac Risk Assessment Formal name: Cardiac Risk Assessment Related tests: Lipid profile; hs-CRP; Lp(a) What is a cardiac risk assessment? This is a group of tests and health factors that have been proven to indicate your chance of having a cardiovascular event such as heart attack or stroke. They have been refined 精炼的to indicate the degree of risk: slight, moderate, or high. 55 What is included in a cardiac risk assessment? Perhaps the most important indicators for cardiac risk are those of your personal health history. Age, hereditary factors, weight, cigarette smoking, blood pressure, exercise history, and diabetes are all important in determining your risk. The lipid profile描绘,轮 廓is the most important blood test for risk assessment. There are imaging tests, non- invasive and invasive侵入的, that may be used in cardiac risk assessment. 56 第二节 心血管疾病主要生化检测 指标 二、心肌损伤标志物 为什么不完全依靠心电图诊断？ 心电图阴性的？ 心电图阳性的？ 57 理想的心肌损伤标志物应满足： 高度心肌特异性，心肌含量高，一旦心肌 损伤便可迅速、大量释放，血中浓度升高即表 明心肌损伤。 能检测早期心肌损伤，在血液中较稳定， 有合适的“诊断窗口期” 。 能估计梗死范围大小，判断预后。 能评估溶栓效果。 58 Cardiac Biomarkers Cardiac biomarkers are substances that are released into the blood when the heart is damaged. Measurement of these biomarkers is used to help diagnose, evaluate, and monitor patients with suspected acute coronary syndrome (ACS). Note: Cardiac biomarkers are not the same tests as those that are used to screen the general healthy population for their risk of developing heart disease. Those can be found under Cardiac Risk Assessment. 59 心肌损伤标志物主要包括： 1. 心肌损伤酶谱 2. 肌红蛋白 3. 肌钙蛋白T和I亚单位 4. 研究中的心肌损伤标志物（脂肪酸结合 蛋白、糖原磷酸化酶同工酶PP，缺血修饰性清 蛋白） 60 Only a few cardiac biomarker tests are routinely used by physicians. The current biomarker test of choice for detecting heart damage is troponin肌钙蛋白. Other cardiac biomarkers are less specific for the heart and may be elevated in skeletal muscle injury, liver disease, or kidney disease. Many other potential cardiac biomarkers are being researched, but their clinical utility has yet to be established. 61 Current cardiac biomarker tests used to help diagnose, evaluate, and monitor patients suspected of having Acute Coronary Syndrome (ACS): CK and CK-MB , Troponin , Myoglobin Additional biomarker tests that may be used to evaluate risk of future cardiac events (prognosis): BNP (or NT-proBNP) , hs-CRP Phased out biomarkers - the tests below are not specific for damage to the heart and are no longer recommended for evaluating patients with suspected ACS: AST , LDH 62 1. 心肌损伤酶谱 (enzyme profile of myocardial injury) 一般指天门冬氨酸氨基转移酶AST 、乳酸脱 氢酶LD 、肌酸激酶CK 、以及后两者同工酶。 63 (1)天门冬氨酸氨基转移酶 (aspartate aminotransferase, AST) 人体内AST分子量约100 kD，在心肌 中含量最高，因此而具有相对心肌分布特异性 。 AMI发生后612 h血液中AST始出现 升高，2448 h达峰值，若无再损伤发生，57 d 恢复正常水平。 64 因其体内分布广泛，多种器官病变均可致血 中水平升高，特异性不高；此外，红细胞亦富含 AST，轻度溶血即可致AST水平非病理性显著升 高。 AST诊断AMI的特异性仅53%。AST分子较 大， AMI发生612 h后血清AST 水平才出现升 高，24 h左右才达峰值，远不能满足尽早干预， 恢复有效血液灌注的要求。 现在建议不再用AST作为心肌损伤标志。 65 (2)乳酸脱氢酶(lactate dehydrogenase, LD)及其同工酶 LD是由肌(muscle, M)型和心(heart, H)型 两种亚单位组成的4聚体，分子量约134 kD。LD 至少有5种同工酶，按电泳条带距阳极的近远， 依次命名为LD1LD5 。 LD广泛存在于各种器官组织胞浆，按含量 多少依次为肝、心、肾、骨骼肌、红细胞、脑等 。 66 命名 亚单亚单 位组组 成 主要分布组织组织 及细细胞 LD1 H4 心肌、红细红细 胞、肾肾皮质质、白细细胞、 肝 LD2 H3, M1白细细胞、肾肾、红细红细 胞、心肌、肝 LD3H2, M2白细细胞、脾、肺、血小板、肝、淋巴 组织组织 等 LD4H1, M3肝、骨骼肌、白细细胞、血小板 LD5M4骨骼肌、肝、血小板 LD1比总LD更具心肌特异性。LD作为心肌损 伤标志物，包括血清LD总活性、LD1同工酶活性 或相对比例测定。 67 临床意义及评价： 由于分子较大，AMI等心肌损伤发生后, 8 12h 血中LD及LD1始出现升高，3d 左右达峰值 ，812d缓慢恢复正常。 LD1主要分布于心肌，因此，心肌损伤时血 中LD以LD1为主，并由此导致LD2的相对比例下 降，出现LD1/ LD21的比值反转(flipped LD isoenzyme ratio)特点。 68 评价： 不能满足AMI早期诊断需要。血中升高出现 时间较迟，同工酶谱检测周期较长。 特异性低。分布广泛，红细胞LD同工酶谱 与心肌相似 ，溶血亦可表现为LD1/ LD21比值 反转。LD活性诊断AMI的特异性仅53%，LD1/ LD2反转特异性亦仅85%90%。 不适宜用作再灌注标志。 不提倡以LD及其同工酶作为心肌损伤标 志。 69 (3) 肌酸激酶 (Creatine Kinase, CK) 催化：肌酸与ATP之间高能磷酸键转移生成 磷酸肌酸和ADP的可逆反应，为肌肉收缩和运输 系统提供能量来源。 70 CK及其同工酶的组织分布 组织 总酶活性(U/g) CK-MM CK-MB CK -BB 骨骼肌 2500 98.9% 1.1% 0.06% 脑 555 0% 2.7% 97.3% 心脏 473 78.7% 20% 1.3% 骨骼肌里几乎都是CK-MM 脑中CK-BB含量明显高于其他组织 心肌是唯一含CK-MB较多的器官。 71 M亚单位存在易被血浆中羧肽酶水解的C-端 赖氨酸残基，因此： 血清CK-MM同工酶存在3种亚型： CK-MM1(无C-端赖氨酸残基) CK-MM2 (1个C-端赖氨酸残基) CK-MM3(含2个C-端赖氨酸残基的原型) 。 同理CK-MB同工酶存在2种亚型： CK-MB1(无C-端赖氨酸残基) CK-MB2(1个C-端赖氨酸残基的原型) 72 测定方法 抗凝剂，可对CK活性产生影响，应以血清为 活性检测标本。 总CK活性测定推荐酶偶联法为参考方法 。 pH为6.76.9时，CK催化磷酸肌酸和ADP生 成肌酸和ATP(逆反应); 在己糖激酶催化下，ATP使葡萄糖磷酸化为6- 磷酸葡萄糖; 再在6-磷酸葡萄糖脱氢酶催化下，氧化 NADP+为NADPH。340nm监测NADPH的生成速 率代表总CK活性。 73 上述第一步反应中生成的肌酸，亦可直 接用双乙酰和-萘酚反应显色，520nm测定 其光密度代表CK活性。但肌酸显色反应不稳 定，并且肌酐等多种血中物质，均可构成干 扰。 74 血清CK-MB活性测定用免疫抑制法: 测定血 清总CK活性后，加入抗M亚单位抗体，抑制CK -MM和CK-MB中M亚单位活性，再测定残留CK 活性，即为CK-BB和CK-MB中B亚单位活性。 由于血清中CK-BB水平通常5g/L，活性25U/L，以及CK-MB%RI 5%， 或CK-MB%升高至4%25%间。 78 在诊断AMI上，CK及CK-MB广泛应用，诊 断性能优于AST和LD及其同工酶。为避免漏诊 现推荐入院时、3、6、9h各测定一次。 AMI发生后612h，CK-MB敏感性为92% 96%。在无典型心电图改变和/或梗死性心绞痛的 患者，约80%可观察到CK及CK-MB升高，有助 于诊断。 其升高幅度和梗死面积有一定相关性。 可用于再灌注和再梗死的判断。 红细胞中无CK及CK-MB，不受溶血干扰。 79 存在问题 各种骨骼肌疾患、中枢神经系统疾患均可致血 清CK活性升高。 分娩出现心肌损伤样CK及CK-MB改变。 某些药物可致CK活性升高。 甲状腺功能紊乱可致血中CK及CK-MB异常。 免疫抑制法测定CK-MB活性受干扰较多。 80 诊断性能的缺点： 不能满足早期诊断要求。 特异性不高。 不能满意的反映微小心肌损伤。 81 When is it ordered? CK-MB is usually ordered along with total CK in persons with chest pain to determine whether the pain is due to a heart attack. It may also be ordered in a person with a high CK to determine whether damage is to the heart or other muscles. 82 Increased CK-MB can usually be detected in heart attack patients about 3-4 hours after onset of chest pain. The concentration of CK-MB peaks in 18-24 hours and then returns to normal within 72 hours. Although CK-MB is a very good test, it has been largely replaced by troponin, which is more specific for damage to the heart. 83 What does the test result mean? If the value of CK-MB is elevated and the ratio of CKMB to total CK (relative index) is more than 2.53, it is likely that the heart was damaged. A high CK with a relative index below this value suggests that skeletal muscles were damaged. 84 2. 肌红蛋白(myoglobin, Mb) Mb为存在于横纹肌(骨骼肌和心肌)胞浆中的 一种氧转运蛋白，约占横纹肌细胞中蛋白的2%， 分子量仅17 kD。 因Mb在心肌中含量较丰富，存在于胞浆中， 分子量较小，故心肌损伤早期即可大量漏出入血。 在AMI发生1h后，血中Mb水平即可增高于参 考范围上限, 412 h达峰值。如无再梗死发生约 2436 h内即降至正常 。 85 测定方法： 血清Mb多采用其单克隆抗体免疫学 方法检测其质量，包括免疫浊度法、荧光标记免 疫法、化学发光或电化学发光法、酶联免疫法等 。可在10 min内完成测定。 (2) 参考范围 血清Mb（免疫法），男性0.1g/L。 不同厂家cTnI试剂盒所用的抗体及检测方法 不同，参考值存在较大差异，不同厂家提供的健 康人群cTnI参考范围上限（第99百分位值） 0.11.01g/L, 诊断AMI的判断值为1.03.5 g/L 。 96 (3) 临床意义及评价 由于高度心肌特异性，为目前公认的AMI最 佳确诊性标志。 血中浓度与梗死范围及预后存在良好的相 关性，可协助判断预后。 诊断窗口期长(cTnT约7d，cTnI10d以上) ，故有利于诊断未及时就诊的AMI。 用于诊断心肌炎、UAP等其他原因所致心 肌微小损伤。 97 存在问题 非理想的早期诊断标志，在AMI发生后6h内 其敏感性低于Mb，也不及CK-MB 。不易发现间 隔较短的再梗死。 虽cTnI更具心肌特异性，但cTnI试剂盒生产 厂家多，抗体和检测方法不同，最低检测限和参 考值存在10倍以上差异。 98 AMI后常用心肌标志物血浆动态变化示意图 99 When is it ordered? The tropon