急性心肌梗死患者PCI术后血浆GSH氧化还原态的变化及其预后关系的研究

发布时间：2018-05-01 18:08

本文选题：急性心肌梗死 + 谷胱甘肽　；参考：《成都医学院》2017年硕士论文

【摘要】：目的通过测定急性ST段抬高性心肌梗死患者接受急诊冠脉介入治疗24h前后血浆中MDA、SOD及GSH氧化还原态的变化,探究不同分组下的STEMI患者氧化应激状态的改变,并初步探讨血浆GSH氧化还原态与急性心肌梗死患者预后之间的关系。方法(1)选取2015年1月至2016年8月于成都医学院第一附属医院心血管内科就诊的首次发病12小时以内并接受经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)且成功开通罪犯血管的急性ST段抬高性心肌梗死患者,共计93例。经皮冠状动脉介入治疗使用常规技术标准执行,并除外癌症、慢性炎症以及其他在24小时内发生的全身感染。入院后参照中华医学会心血管病学分会等制订的《急性心肌梗死诊断和治疗指南》对患者进行规范化治疗,主要措施包括经皮冠状动脉支架植入术以及术后抗凝、抗血小板治疗、纠正心律失常、心力衰竭以及对症支持治疗等。(2)术前和术后24h分别抽取患者肘静脉血5ml。采用酶联免疫吸附法检测血浆MDA,SOD含量,采用酶标微板法检测血浆中GSH、GSSG含量,并计算GSH/GSSG比值以及GSH/GSSG氧化还原电势Eh(GSH/GSSG)。(3)按照患者心梗部位分不同为前壁组和非前壁组,按照血管狭窄数目不同分为单只病变组、双支病变组和三支病变组,比较组间患者血浆氧化应激水平和GSH氧化还原态的差异。(4)对93例患者连续随访180天,按照是否发生心血管不良事件(MACE事件)分为无MACE组72例和MACE组21例。比较两组患者血浆GSH氧化还原态的差异。(5)初步评价Eh(GSH/GSSG)对心肌梗死患者近期预后的诊断价值。探究并寻找心肌梗死患者PCI术后发生MACE事件的独立危险因素。结果(1)与PCI术前相比,PCI术后24h,血浆MDA水平增加(p0.05)、SOD水平降低(p0.05),GSH、GSH/GSSG水平降低(p0.05),GSSG水平无明显差异(p0.05),Eh(GSH/GSSG)水平升高(p0.05)。(2)PCI术前,与非前壁组相比,前壁组血浆MDA、SOD水平无明显差异(p0.05),GSSG、GSH/GSSG水平无明显差异(p0.05),GSH水平较低(p0.05),Eh(GSH/GSSG)水平更高(p0.05)。PCI术后24h,与非前壁组相比,前壁组血浆MDA、SOD水平仍无明显差异(p0.05),GSH、GSH/GSSG水平较低(p0.05),GSSG无明显差异(p0.05),Eh(GSH/GSSG)仍然处于更高水平(p0.05)。PCI术前,单支病变组、双支病变组和三支病变组两两对比,血浆GSH、GSSG、GSH/GSSG和Eh(GSH/GSSG)水平均无明显差异(p0.05),PCI术后24h再次对比,血浆MDA、SOD无明显差异(p0.05),GSH、GSSG、GSH/GSSG水平也无明显差异(p0.05),但Eh(GSH/GSSG)水平差异显著(p0.05),且随病冠脉变数目的增加,Eh(GSH/GSSG)水平也相应升高。(3)与无MACE组相比,MACE组术前血浆MDA、SOD、GSH、GSSG、GSH/GSSG和Eh(GSH/GSSG)水平均无明显差异(p0.05)。PCI术后24h,MACE组较无MACE组GSSG水平仍无明显差异(p0.05),而GSH、GSH/GSSG水平更低(p0.05),Eh(GSH/GSSG)水平更高(p0.05)。ROC曲线得到预测MACE事件Eh(GSH/GSSG)的最佳临界值为-122.5m V,此时灵敏度71%,特异性76%。在Kaplan-Meier生存分析中,高危组与低危组相比,MACE发生率差异显著(p0.05),30天内的MACE发生率差异显著(p0.05),30天后两组MACE发生率无明显差异(p0.05)。多变量Cox比例风险分析中,24小时Eh(GSH/GSSG)"g-122.5m V(HR 4.25,p=0.005,95%Cl 1.56-11.55),慢性肾脏疾病(HR 3.70,p=0.008,95%CI 1.40-9.76),左室射血分数(5%HR 0.94,p=0.005,95%CI 0.90-0.98)。结论(1)STEMI患者PCI术后24h,外周血浆SOD活力降低,MDA含量和Eh(GSH/GSSG)水平升高,表明心肌缺血再灌注损伤造成了自由基爆发,发生脂质过氧化的同时消耗了SOD、GSH,GSH氧化还原态向氧化方向偏移,氧化应激加重。(2)前壁STEMI患者无论PCI术前还是术后24h,与非前壁患者相比血浆GSH水平更低,Eh(GSH/GSSG)水平更高。表明梗死部位在前壁会造成更严重的氧化应激和缺血再灌注损伤。PCI术前不同数目冠脉病变患者GSH氧化还原状态无明显差异,PCI术后24h随病冠脉变数目增加,Eh(GSH/GSSG)水平递增。表明冠脉病变数目与缺血再灌注后的氧化应激水平呈正相关。(3)外周血浆Eh(GSH/GSSG)水平可用于接受PCI治疗的STEMI患者的危险分层。PCI术后24h血浆Eh(GSH/GSSG)"g-122.5m V的STEMI患者的MACE风险增加,Eh(GSH/GSSG)对STEMI患者PCI术后MACE具有独立预测价值。
[Abstract]:Objective to investigate the changes of MDA, SOD and GSH redox state in the plasma of acute ST segment elevation myocardial infarction (AMI) patients before and after the emergency coronary intervention therapy (24h), and to explore the relationship between the plasma GSH redox state and the prognosis of patients with acute myocardial infarction. (1) from January 2015 to August 2016, a total of 93 patients with acute ST segment elevation myocardial infarction (percutaneous coronary intervention, PCI) for the first time in the First Affiliated Hospital of Chengdu Medical College were selected for the first 12 hours of medical treatment in the Department of cardiovascular medicine. Interventional therapy is performed with conventional technical standards, excluding cancer, chronic inflammation, and other systemic infections within 24 hours. A guideline for the diagnosis and treatment of acute myocardial infarction, which is formulated by the CMA cardiovascular disease branch, is standardized after admission to patients. The main measures include percutaneous coronary stent implantation. Anticoagulant, antiplatelet therapy, arrhythmia, heart failure, and symptomatic support therapy were used. (2) the plasma 5ml. was detected by enzyme linked immunosorbent assay (ELISA) in the elbow vein blood before and after 24h, and the content of MDA and SOD was detected by enzyme linked immunosorbent assay. The content of GSH and GSSG in blood plasma was detected by the enzyme labeled microplate method, and the GSH/GSSG ratio and GSH/GSSG were calculated. Redox potential Eh (GSH/GSSG). (3) the patients were divided into the anterior wall group and the non anterior wall group according to the location of the patients' myocardial infarction. According to the number of vascular stenosis, they were divided into single lesion group, double branch lesion group and three pathological group. The difference of plasma oxidative stress level and GSH redox state were compared between the two groups. (4) 93 patients were followed up for 180 days, according to the results. No cardiovascular events (MACE events) were divided into 72 cases without MACE and 21 cases in group MACE. The difference between the plasma GSH redox states of the two groups was compared. (5) the diagnostic value of Eh (GSH/GSSG) for the short-term prognosis of myocardial infarction patients was preliminarily evaluated. The independent risk factors of MACE event after PCI operation in patients with myocardial infarction were explored and found (1) Compared with 24h, plasma MDA level increased (P0.05), SOD level decreased (P0.05), GSH, GSH/GSSG level decreased (P0.05), GSSG level had no significant difference (P0.05) and increased level (P0.05). (2) there was no significant difference (2) before the operation, there was no significant difference between the anterior wall group and the anterior wall group. P0.05), the level of GSH was lower (P0.05), and the level of Eh (GSH/GSSG) was higher (P0.05) after.PCI. Compared with the non anterior wall group, there was no significant difference in plasma MDA and SOD levels in the anterior wall group (P0.05). The levels of plasma GSH, GSSG, GSH/GSSG and Eh (GSH/GSSG) were not significantly different in the three group of pathological changes (P0.05). There was no significant difference in plasma MDA and SOD (P0.05) after PCI, but there was no significant difference in the level of SOD, but there was no significant difference in the level of GSH and SOD. (3) compared with the non MACE group, there was no significant difference in plasma MDA, SOD, GSH, GSSG, GSH/GSSG and Eh (GSH/GSSG) before operation in group MACE (P0.05).PCI after operation (P0.05). The best critical value of Eh (GSH/GSSG) was -122.5m V, at this time the sensitivity was 71%, and the specificity 76%. was in the Kaplan-Meier survival analysis. Compared with the low risk group, the incidence of MACE had a significant difference (P0.05), and the occurrence of MACE within 30 days was significant (P0.05), and there was no significant difference between the two groups of MACE (P0.05) in 30 days. 2 4 hours Eh (GSH/GSSG) "g-122.5m V (HR 4.25, p=0.005,95%Cl 1.56-11.55), chronic renal disease (HR 3.70, p=0.008,95%CI 1.40-9.76), left ventricular ejection fraction (5%HR 0.94, p=0.005,95%CI). The injury caused the free radical eruption, and the lipid peroxidation caused SOD, GSH, GSH redox state to shift to the oxidation direction, and the oxidative stress was aggravated. (2) the plasma GSH level was lower and the level of Eh (GSH /GSSG) was higher in the anterior wall STEMI patients, no matter before or after PCI, and the level of Eh (GSH /GSSG) was higher than those of the non anterior wall patients. There was no significant difference in the redox state of GSH in patients with different number of coronary lesions before.PCI with severe oxidative stress and ischemia-reperfusion injury. The number of coronary artery changes and the level of Eh (GSH/GSSG) increased gradually after PCI, indicating that the number of coronary lesions was positively correlated with the level of oxidative stress after ischemia reperfusion. (3) the level of plasma Eh (GSH/GSSG) in peripheral plasma could be found. The risk of 24h plasma Eh (GSH/GSSG) "g-122.5m V's STEMI patient's MACE risk increased after the dangerous stratified.PCI for the STEMI patients receiving PCI treatment, and Eh (GSH/GSSG) had an independent predictive value for the postoperative patients.

【学位授予单位】：成都医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R542.22

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