發(fā)布時間：2018-05-05 07:23

  本文選題：金屬基質(zhì)蛋白酶2 + 急性冠脈綜合征�。� 參考：《大連醫(yī)科大學(xué)》2016年碩士論文

【摘要】：研究背景和研究目的:金屬基質(zhì)蛋白酶是一類在降解細胞外基質(zhì)過程中起重要調(diào)節(jié)作用的內(nèi)源性酶家族,具有鋅依賴性。金屬基質(zhì)蛋白酶2(matrix metalloproteinases,MMP2)是其家族中的一種,又名明膠酶A,在病理狀態(tài)下參與了動脈粥樣硬化斑塊的形成、斑塊不穩(wěn)定、冠脈血管的再狹窄、高血壓、心室重塑、心力衰竭等過程。且已有研究發(fā)現(xiàn)MMP2-1306C/T的基因多態(tài)性通過轉(zhuǎn)錄水平的調(diào)節(jié)影響MMP2水平的表達進而引起患冠心病及急性冠脈綜合征(acute coronary syndrome,ACS)的風(fēng)險增加。本研究主要通過對ACS患者MMP2-1306C/T基因位點進行檢測獲得分型,并探討此位點的多態(tài)性對ACS患者冠脈血管狹窄病變支數(shù)及其不良預(yù)后有無影響。研究對象及研究方法:收集在大連醫(yī)科大學(xué)附屬第一醫(yī)院心臟急重癥科和冠心病一科2013年3月至11月期間符合ACS診斷的住院患者302例,對其進行基因檢測得到基因分型。詳細收集患者的臨床資料:化驗結(jié)果、心臟彩超(左室內(nèi)徑及射血分?jǐn)?shù))、冠脈造影結(jié)果,并對患者進行臨床隨訪至少一年,隨訪的主要終點事件是聯(lián)合終點事件,即死亡、再發(fā)心絞痛、心肌梗死、心力衰竭、心律失常的復(fù)合終點;次要終點是在隨訪期間發(fā)生的死亡、復(fù)發(fā)心絞痛、再梗、心力衰竭、心律失常。除去在基因檢測過程中檢測失敗的4例和失訪的患者60例,最終入選238例。對其進行基因多態(tài)性分析并評估MMP2-1306C/T基因多態(tài)性對其預(yù)后有無影響。研究結(jié)果:1.基因型分布:238例入選的患者中,其中CC組患者共196例占82.4%,CT組患者共40例占16.8%,TT組患者共2例占0.8%,C等位基因的頻率為90.8%,T等位基因的頻率為9.2%。2.冠狀動脈狹窄病變支數(shù)的比較:單、雙、多支血管狹窄病變的比例在CC組和CT/TT組兩組內(nèi)均呈現(xiàn)逐漸減少的趨勢,但在兩組間單支57.8%vs 56.2%、雙支30.5%vs 31.3%、三支11.7%vs 12.5%,差異均無統(tǒng)計學(xué)意義。3.臨床不良預(yù)后的比較:對患者隨訪23.2±1.5個月,接近一半的患者發(fā)生了聯(lián)合終點事件,其中再發(fā)心絞痛的患者所占的比例最高,在CC組占44.9%,CT/TT組占23.8%,其次是心力衰竭,死亡、再梗、心律失常所占的比例則較低。CC組與CT/TT組相比再發(fā)心絞痛的頻率明顯增加,P為0.006,具有顯著差異性。聯(lián)合終點事件發(fā)生率及死亡、再梗、心律失常、心力衰竭等單個事件的發(fā)生率的差異性均無統(tǒng)計學(xué)意義。其中CC基因型4例發(fā)生了再次心肌梗死的患者中有3例實行了PCI術(shù),CT/TT基因型實行PCI術(shù)的患者中無一例發(fā)生再次心肌梗死。4.院外藥物服用情況比較:其中阿司匹林和他汀類藥物的服用率較高,在兩組間均達到了80%以上。β受體阻滯劑在CC組的服用率為72.96%,CT/TT組為85.71%高于CC組。氯吡格雷、ACEI/ARB的服用率稍低。但藥物在兩組間比較差異均未有統(tǒng)計學(xué)意義5.將再發(fā)心絞痛作為因變量,年齡、性別、是否心梗、吸煙、飲酒、高血壓、糖尿病、血脂水平、空腹血糖、介入治療、住院期間服用阿司匹林、氯吡格雷、ACEI/ARB、β受體阻滯、他汀類藥物及院外繼續(xù)服用這些藥物等結(jié)果如下作為自變量,行二分類Logistic回歸分析,結(jié)果顯示甘油三脂的含量、高密度脂蛋白的含量、空腹血糖的水平、AMI、MMP2-1306CC對再發(fā)心絞痛呈現(xiàn)相關(guān)性。結(jié)論:1.ACS患者中MMP2-1306C/T的基因表型多為CC型,CC基因型和C等位基因的頻率顯著高于CT/TT基因型和T等位基因的頻率,與以往國內(nèi)外研究一致。2.MMP2-1306CC基因型的患者復(fù)發(fā)心絞痛頻率增加,CC基因型是ACS患者發(fā)生復(fù)發(fā)心絞痛的危險因素,表明CC基因型可能增加了AS斑塊的不穩(wěn)定性,CC基因型PCI術(shù)后再發(fā)心肌梗死的概率可能也會增加。但該基因型對患者心室重塑的影響未發(fā)現(xiàn)有明確關(guān)聯(lián)。3.不同MMP2-1306C/T基因表型的ACS患者冠脈血管狹窄病變支數(shù)無明顯差異。4.MMP2-1306CC、甘油三脂水平增高、高密度脂蛋白水平降低以及心肌梗死是ACS患者發(fā)生復(fù)發(fā)心絞痛的危險因素,空腹血糖水平也是復(fù)發(fā)心絞痛的相關(guān)因素。
[Abstract]:Research background and purpose: metal matrix protease is an endogenous enzyme family which plays an important regulatory role in the degradation of extracellular matrix. Metal matrix protease 2 (matrix metalloproteinases, MMP2) is one of its family, also known as gelase A, and is involved in atherosclerotic plaques in the pathological state. The formation of block, plaque instability, coronary artery restenosis, hypertension, ventricular remodeling, heart failure and other processes. And it has been found that the gene polymorphism of MMP2-1306C/T affects the expression of MMP2 level through the regulation of transcriptional levels and thus causes increased risk of coronary heart disease and acute coronary syndrome (acute coronary syndrome, ACS). The study mainly through the detection of the MMP2-1306C/T gene loci of ACS patients, and explore the polymorphism of this site on the number of coronary vascular stenosis and its adverse prognosis in patients with ACS. Research objects and methods: collected at the First Affiliated Hospital of Dalian Medical University, the heart emergency and coronary heart disease one family in 2013 3 302 hospitalized patients diagnosed with ACS during the period from month to November were genotyping. The clinical data of the patients were collected in detail: test results, cardiac color Doppler (left ventricular diameter and ejection fraction), coronary angiography results, and the patients were followed up for at least one year, and the main end point of follow-up was the joint endpoint event. Death, angina, myocardial infarction, heart failure, arrhythmia, secondary end point was death during the follow-up period, recurrent angina, re infarction, heart failure, arrhythmia. 4 cases of failure and 60 patients in the process of gene detection were removed, and 238 cases were finally selected. Analysis and assessment of the effect of MMP2-1306C/T gene polymorphism on its prognosis: 1. genotype distribution: among 238 patients, 196 cases in group CC were 82.4%, 40 in group CT were 16.8%, 2 in group TT were 0.8%, and C alleles were 90.8%, and the frequency of T alleles was 9.2%.2. coronary stenosis branch. The ratio of single, double and multiple vascular stenosis showed a gradual decrease in the two groups in group CC and group CT/TT, but in the two groups, single branch 57.8%vs 56.2%, double branch 30.5%vs 31.3%, and three 11.7%vs 12.5%, the difference was not statistically significant in.3. clinical adverse prognosis: the patients were followed up for 23.2 + 1.5 months, close to half of the patients. The proportion of patients with angina pectoris had the highest proportion, 44.9% in group CC and 23.8% in group CT/TT, followed by heart failure, death, re infarction, and arrhythmia, the rate of recurrent angina was significantly increased in the lower.CC group compared with the CT/TT group, and P was 0.006, with a significant difference. The joint endpoint incident occurred. There was no significant difference in the incidence of single events such as birth rate and death, re infarction, arrhythmia, and heart failure. Among the 4 patients with CC genotype, 3 of the patients with re myocardial infarction were performed PCI, and none of the CT/TT genotype patients with PCI were compared with.4. for re myocardial infarction. The use of aspirin and statins was higher than 80% in the two groups. The use rate of beta blockers in group CC was 72.96%, and 85.71% in group CT/TT was higher than that in group CC. The use rate of clopidogrel and ACEI/ARB was slightly lower. However, there was no statistically significant difference between the two groups 5.. Age, sex, myocardial infarction, smoking, alcohol, hypertension, diabetes, blood lipid levels, fasting blood glucose, interventional therapy, taking aspirin, clopidogrel, ACEI/ARB, beta blocker, statins, and continuing to take these drugs as independent variables, two classified Logistic regression analysis, the results showed glycerin. The content of three fat, the content of high density lipoprotein, the level of fasting blood glucose, AMI and MMP2-1306CC were related to the angina pectoris. Conclusion: the gene phenotype of MMP2-1306C/T in 1.ACS patients is mostly CC, the frequency of CC genotypes and C alleles is significantly higher than that of CT/TT genotypes and T alleles, which is consistent with the previous studies at home and abroad. The frequency of recurrent angina in the 2-1306CC genotype was increased. The CC genotype was a risk factor for recurrent angina in ACS patients, indicating that the CC genotype may increase the instability of AS plaque, and the probability of reperfusion after CC genotype PCI may also increase. However, the effect of this genotype on ventricular remodeling is not found to be clear. There was no significant difference in the number of coronary artery stenosis in ACS patients with different MMP2-1306C/T gene phenotypes associated with.3.,.4.MMP2-1306CC, high level of glycerol three, low level of high-density lipoprotein and myocardial infarction as a risk factor for recurrent angina in ACS patients. Fasting blood glucose level was also a related factor for recurrent angina pectoris.

【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R541.4

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