【作者】 张涛；

【导师】 郝玉明；

【作者基本信息】 河北医科大学 ， 内科学， 2005， 硕士

【摘要】 目的:不稳定型心绞痛(UA)是急性冠脉综合征(ACS)中最常见的一种类型,试验报告ACS 住院患者中48%是UA。研究表明UA 由冠脉内粥样斑块破裂、内皮功能受损及随后产生的血小板粘附聚集、凝血因子激活和血栓形成,引起冠状动脉阻塞所致。其中斑块的不稳定性是产生UA 的始动因素。局部炎症是斑块不稳定和破裂的重要基础。炎症过程中最具有标志性的因子C 反应蛋白(CRP)被认为与动脉粥样硬化、冠状动脉疾病的发生发展和预后有密切关系。CRP 主要由肝细胞合成,他在人体炎症反应后6-48h 内上升,故又称为肝细胞急性相蛋白,细胞因子IL-6 是其主要诱发因子。大量研究表明CRP 不仅可反应斑快稳定性预示斑块破裂,而且对UA 患者的短期和长期预后有重要估测价值。近些年来发现高敏C 反应蛋白(hsCRP)比CRP 更能精确、客观反映心血管事件的发生。目前研究表明基质金属蛋白酶(MMPs)与斑块稳定性密切相关。MMPs 是细胞外基质降解的重要介质。MMPs家族是一类含锌离子的内源性蛋白水解物。UA 患者血清和斑块纤维帽中MMP-9 的浓度明显增高,表明其与斑块稳定性有关。研究表明MMP-9 通过降解粥样斑块的纤维帽成分,导致或加速斑块的破裂。内皮功能完整性对于维持血管的正常功能是至关重要的。一氧化氮(NO)能保护内皮功能。动脉粥样硬化患者内皮细胞功能有不同程度的受损,NO 的合成更多还原

【Abstract】 Objective: Unstable angina（UA） is commonest type ofacute coronary syndrome（ACS）. EARISA trial reported that48% of the patients hospitalized for ACS was diagnosed as UA.Cardiovascular events typically arise from the disruption of theatherosclerotic plaques that contain numerous inflammatorycells. Inflammatory cells release cytokines that degradeextracellular matrix in the fibrous cap of atherosclerotic plaques.Activated inflammatory cells produce tissue factor thatpromotes thrombus formation by disrupted atheroma. Coronarythrombosis is now generally recognized as the precipitatingevent in the transition from stable to acute ischemic heart diease,manifested by UA, acute myocardial infarction, and suddendeath from coronary causes. Concentrations of C-reativeprotein（CRP） are directly correlated with the presence andseverity of coronary, cerebral, and peripheral arterialatherosclerosis. CRP is a representative acute phase reactantprotein. CRP is synthesized by liver and modulated by IL-6.Increases in the plasma concentrations of CRP have beenobserved in patients with severe UA. A plasma concentration ofCRP above 3 mg/l was associated with a significantly worseprognesis in patients admitted to hospital with UA. Furthermore,high-sensitivity CRP（hsCRP） is better to predict the risk of theheart events. Matrix metalloproteinases （MMPs） are a family ofZn²⁺ -dependent endopeptidases capable of cleaving componentsof extracellular matrix . MMP-9 plays a very important role inheart events. Evidences suggest that MMP-9 activity mayfacilitate atherosclerosis, plaque destabilization, and plateletaggregation. The endothelium plays a central role in maintainingcardiovascular homeostasis via the production and release ofvasoactive mediators such as endothelium-derived relaxingfactor（EDRF） and nitricoxide（NO）. Endothelium dysfunctionthat produces less NO plays an essential role in thepathophysiology of coronary heart disease（CHD） especiallywith the initial and developmental process of atherosclerosis andthrombosis via the following possible mechanisms:（1）causingdefects in coronary artery vasomotion,（2） promoting the processof coronary arterial wall remodeling,（3） facilitating plateletactivation and aggregation,（4） accelerating monocyte andneutrophils activation and adherence. HMG-CoA reductaseinhibitors （stains） can reduce heart events of the patients withCHD. Stains can lower lipid, improve endothelium function,prohibit platelet activation and aggregation, stabilize plaque andprevent inflammatory cells produce. We study the effect ofdifferent-dose atorvastatin in early stage of the UA patients tofind whether higher dose atorvastatin is better than lower doseatorvastatin and their side effect.Method: A total of 90 patients（mean age 58.8+12 years,men 65, women 25） were selected consecutivly from September2003 to Octorber 2004. The inclusion criteria include as thefollowings: chest discomfort happen more and last longer in amonth and chest discomfort occur with a duration of at least 15minutes and with the most recent occurrence ≤24 hours beforehospital admisson; the diagnosis of UA required new ordynamic ST-wave or T-wave changes in at least 2 contiguousECG leads or a new wall motion or myocardial perfusionabnormality and no elevation in the serum creatine kinase. Thecriteria for exclusion include a myocardial infarction within theprevious month, coronary artery bypass surgery within thepreceding 3 months, revascularization by coronary catheterintervention within the preceding 6 months, an elevated creatinekinase, intercurrent inflammatory or neoplastic conditions likelyto be associated with an acute-phase response, valvular heartdisease, NYHA cardiac function classification≥3, patient’sserum transaminase levels increase to >3 times the upper limitof normal and using HMG-CoA reductase inhibitors recently. Ifa patient develops muscle pain, weakness, or tenderness inassociation with a serum creatine kinase level>10 times upperlimit of normal, the study medication is discontinued. Patientswere randomized to three groups: group 1（28 patients） taking noatorvastatin（lipitor）; group 2（32 patients） taking lipitor 10mg/d;group 3（30 patients） taking lipitor 20mg/d. All patients weretaking aspirin, nitrate, angiotensin converting enzyme inhibitor,Low Molecular Heparin,β-blocker if they needed. Bloodsamples of all the cases was got after 12 hours fasting afterhospitalized and 10 days later of treatment. Then the serum orplasma was separated and put into laboratory for storage at–80 ℃. All the sample was tested TC,TG,HDL-C,LDL-C,ALT,CK,NO,MMP-9 and hsCRP. A SAS software was used forstatistical analysis, and p value ≤0.05 was consideredstatistically significant.Results: Baseline Characteristics of the Patients did notdiffer among the 3 groups. Ten days later compared with controlgroup, lipitor（10 mg/d） and lipitor（20 mg/d） was associated witha great reduction in TC and LDL-C （P<0.05）; Lipitor （20mg/d）had a greater reduction in TC and LDL-C than lipitor（10mg/d）（P<0.05）. After 10 days of treatment,TG was graduallyreduced and HDL-C and NO was gradually increased with theincreasing dose of lipitor, but there was no significantlydifferent in the 3 groups（P>0.05）. There is no significantlydifferent in CK of the 3 groups after 10 days treatment.Compared with control group, lipitor（10 mg/d） and lipitor（20mg/d） was associated with a great reduction in MMP-9 （P<0.05）after 10 days treatment; Lipitor （20mg/d） had a greater reductionin MMP-9 than lipitor（10 mg/d）（P<0.05）. Compared withcontrol group, lipitor（10 mg/d） and lipitor（20 mg/d） wasassociated with a great reduction in hsCRP（P<0.05） after 10days treatment but there is no different in hsCRP between thetwo group. Compared with control group , lipitor（10 mg/d）and lipitor（20 mg/d） was associated with a great increasing in更多还原