抗炎因子白介素-37血浆水平与急性冠脉综合征的关系

发布时间：2018-05-08 01:15

本文选题：冠心病 + ACS　；参考：《河北医科大学》2017年硕士论文

【摘要】：目的:冠状动脉粥样硬化性心脏病是一个常见的心血管疾病,每年死于心血管疾病的人数多于任何其它死因。在2012年有1750万人死于心血管疾病,占全球死亡总数的31%。这些死者中,估计740万人死于冠心病,670万人死于中风,但其确切机制尚不清楚。以往认为高血压、高脂血症、肥胖、糖尿病、吸烟等危险因素与动脉粥样硬化相关,然而,最近的研究表明,动脉粥样硬化的发病机制可能与多种因素引起的慢性炎症相关。炎症因子在动脉粥样硬化斑块、血栓形成、血小板聚集及各种并发症中发挥作用,进而出现临床急性心血管事件。既往的研究重点关注促炎因子的作用,而随着抗炎因子的发现,探讨冠状动脉粥样硬化保护性因子及多功能因子成为近年来的研究热点。白介素-37(Interleukin-37,IL-37)是2000年发现的白介素家族成员,其显示出了强大的抗炎作用,并发现其与多种人类炎症性疾病相关。2011年Broaschi等人在人类的冠状动脉和颈动脉粥样硬化斑块的泡沫细胞中发现了IL-37,提示IL-37参与了动脉粥样硬化性疾病的发生及发展。然而,血浆IL-37在急性冠状动脉综合征患者(Acute coronary syndrome,ACS)中的水平还有待研究。本研究主要探讨在ACS患者中IL-37的血浆水平与促炎因子白介素-18(Interleukin-18,IL-18)、超敏C反应蛋白(C Reactive Protein,CRP)水平及冠脉病变程度的关系。方法:2016年1月至2016年12月因胸闷、胸痛等症状就诊于河北医科大学第二医院的符合纳入标准的患者作为研究对象。根据患者的症状、心电图、血清超敏肌钙蛋白及我院冠状动脉造影检查分为对照组、稳定型心绞痛及不稳定型心绞痛患者以及急性心肌梗死患者,每组25例。所有急性心肌梗死患者在入院时即行静脉采血,其余患者在入院次日清晨空腹采集。同时收集标本对应患者的一般情况和相关临床资料。常规检测脑钠肽(Brain Natriuretic Peptide,BNP)、左室舒张末径(Left Ventricular End Diastolic Diameter,LVEDD)、左室射血分数(Left Ventricular Ejection Fraction,LVEF)、心肌肌钙蛋白(Cardiac troponin,c TNI)、心肌激酶(Creatine kinase isoenzyme,CK-MB)、肌酐(Creatinine,Cr)、CRP、总胆固醇(Total Cholesterol,CHOL)、甘油三酯(Triglyceride,TG)、低密度脂蛋白胆固醇(Low Density Lipoprotein,LDL)以及根据患者冠状动脉造影术结果而得出的冠脉Gensini评分;用酶联免疫吸附法(Enzyme-1inked immunosorbentassay,ELISA)检测血清IL-37、IL-18。结果:1基本资料分析:患者性别、年龄、Cr、CHOL、TG、LDL、高血压、糖尿病以及服药史等基本资料在对照组、稳定组、不稳定组以及心梗组之间差异无统计学意义。心梗组的LVEF较对照组、稳定组、不稳定组降低,且差异具有统计学意义(P0.05)。LVEF在对照组、稳定组及不稳定组之间差异无统计学意义。心梗组LVEDD、BNP、c TNI、CRP、Gensini评分、CK-MB较对照组、稳定组、不稳定组明显升高,且差异有统计学意义(P0.05)。LVEDD、BNP、c TNI、CRP、Gensini评分、CK-MB在对照组、稳定组、不稳定组之间差异无统计学意义。2 IL-37及IL-18的血浆水平和组内比较:IL-37的四组血浆水平分布均为非正态分布,故应用中位数与四分位间距表示。对照组、稳定组、不稳定组、心梗组的血浆IL-37水平分别为39.71(35.85,46.10)pg/ml、35.92(32.20,58.35)pg/ml、54.81(34.10,60.33)pg/ml、55.64(37.90,62.50)pg/ml。进一步分析发现:心梗组与不稳定组IL-37血浆水平无差异(P0.05),对照组与稳定组IL-37血浆水平无差异(P0.05),但是心梗组和不稳定组IL-37血浆水平明显高于对照组、稳定组,且具有统计学差异(P0.05)。IL-18的四组血浆水平分布均为非正态分布,故应用中位数与四分位间距表示。对照组、稳定组、不稳定组、心梗组的血浆IL-18水平分别为382.69(290.71,662.03)pg/ml、475.76(253.52,839.56)pg/ml、835.17(447.52,1514.82)pg/ml、1437.96(697.13,2473.42)pg/ml。进一步分析发现:心梗组与不稳定组IL-18血浆水平无差异(P0.05),对照组与稳定组IL-18血浆水平无差异(P0.05),但是心梗组和不稳定组IL-18血浆水平明显高于对照组、稳定组,且具有统计学差异(P0.05)。3相关分析:临床资料与IL-37之间的相关性分析显示:IL-37浓度与BNP、c TNI、Cr、CK-MB、LVEDD、CHOL、TG、LDL、Gensini评分无明显相关,与CRP之间具有正相关性(r=0.26,P=0.008),与LVEF之间具有负相关性(r=-0.51,P0.001)。IL-37与IL-18之间的相关性的分析:经Spearman相关分析,血清中IL-37与IL-18具有正相关性(r=0.21,P=0.04)。结论:IL-37血浆水平在ACS组中明显高于稳定组及对照组,且具有统计学差异(P0.05),IL-37与IL-18、CRP具有正相关性,提示IL-37是冠心病相关的炎症因子,有可能成为ACS患者新型的炎症生物标志物。
[Abstract]:Objective: coronary atherosclerotic heart disease is a common cardiovascular disease. The number of deaths from cardiovascular disease is more than any other cause of death every year. In 2012, 17 million 500 thousand people died of cardiovascular disease, which accounted for 31%. of the total number of deaths in the world. An estimated 7 million 400 thousand died in coronary heart disease and 6 million 700 thousand died of stroke, but the exact mechanism was It's not clear that risk factors such as hypertension, hyperlipidemia, obesity, diabetes, smoking and other risk factors are associated with atherosclerosis. However, recent studies have shown that the pathogenesis of atherosclerosis may be associated with chronic inflammation caused by a variety of factors. Inflammatory factors are in atherosclerotic plaques, thrombosis, platelet aggregation, and each other. Clinical acute cardiovascular events are involved in the complications. Previous studies focus on the role of pro-inflammatory factors. With the discovery of anti-inflammatory factors, the study of the protective factors and multifunction factors of coronary atherosclerosis has become a hot topic in recent years. Interleukin-37 (IL-37) -37 (IL-37) was found in 2000. Members of the mediator family showed strong anti-inflammatory effects and found that they were associated with a variety of human inflammatory diseases.2011 Broaschi and others found IL-37 in the human coronary and carotid atherosclerotic plaque foam cells, suggesting that IL-37 was involved in the occurrence and development of atherosclerotic disease. However, plasma IL-37 The level of Acute coronary syndrome (ACS) in patients with acute coronary syndromes (ACS) remains to be studied. This study focuses on the relationship between the plasma level of IL-37 in ACS patients and the proinflammatory factor -18 (Interleukin-18, IL-18), the hypersensitivity C reactive protein (C Reactive) level, and the degree of coronary artery disease. Methods: January 2016 By December 2016, patients who were diagnosed with chest tightness and chest pain were treated in the second hospital of Hebei Medical University as subjects. According to the symptoms, electrocardiogram, serum hypersensitivity troponin, and our coronary angiography, the patients were divided into control group, stable angina and unstable angina pectoris, and acute myocardium. Patients with infarction were 25 in each group. All patients with acute myocardial infarction were collected at the time of admission to the hospital. The rest of the patients were collected on the fasting morning on the next day. At the same time, the general situation and related clinical data of the patients were collected. The Brain Natriuretic Peptide (BNP) and the left ventricular end diastolic diameter (Left Ventricular End Diastol) were routinely examined. IC Diameter, LVEDD), left ventricular ejection fraction (Left Ventricular Ejection Fraction, LVEF), cardiac troponin (Cardiac troponin, C TNI), myocardial kinase, triglyceride, triglyceride, low density lipoprotein cholesterol Y Lipoprotein, LDL) and coronary Gensini score based on patients' coronary angiography; serum IL-37 and IL-18. results were detected by enzyme linked immunosorbent assay (Enzyme-1inked Immunosorbentassay, ELISA): 1 basic data analysis: patient sex, age, Cr, CHOL, TG, hypertension, diabetes and medicine history. In the control group, there was no significant difference between the stable group, the unstable group and the myocardial infarction group. The LVEF of the myocardial infarction group was lower than the control group, the stable group and the unstable group, and the difference was statistically significant (P0.05).LVEF in the control group. The difference between the stable group and the unstable group was not statistically significant. The myocardial infarction group was LVEDD, BNP, C TNI, CRP, Gensini score and CK-MB. The control group, the stable group and the unstable group were significantly higher, and the difference was statistically significant (P0.05).LVEDD, BNP, C TNI, CRP, Gensini score, CK-MB in the control group, the stable group, the unstable group was not statistically significant.2 IL-37 and IL-18 plasma level and intra group comparison: the four groups of IL-37 were in the non normal distribution, so application In the control group, the stable group and the unstable group, the plasma IL-37 level of the myocardial infarction group was 39.71 (35.85,46.10) pg/ml, 35.92 (32.20,58.35) pg/ml, 54.81 (34.10,60.33) pg/ml, 55.64 (37.90,62.50) pg/ml. further analysis found that there was no difference between the plasma level of IL-37 in the myocardial infarction group and the unstable group (P0.05), the control group and the stable group. The plasma level of IL-37 was not different (P0.05), but the plasma level of IL-37 in the myocardial infarction group and the unstable group was significantly higher than that of the control group. The four groups of plasma levels in the stable group, with statistical difference (P0.05).IL-18, were all non normal distribution, so the median and four division intervals were shown. The control group, the stable group, the unstable group, the plasma IL-18 of the myocardial infarction group. The level of 382.69 (290.71662.03) pg/ml, 475.76 (253.52839.56) pg/ml, 835.17 (447.521514.82) pg/ml, 1437.96 (697.132473.42) pg/ml. further analysis showed that there was no difference in the level of IL-18 plasma in the myocardial infarction group and the unstable group (P0.05), and there was no difference between the control group and the stable group (P0.05), but the blood of the myocardial infarction group and the unstable group were blood. The plasma level was significantly higher than that of the control group, and the stable group was statistically different (P0.05).3 correlation analysis. The correlation analysis between clinical data and IL-37 showed that the concentration of IL-37 had no significant correlation with BNP, C TNI, Cr, CK-MB, LVEDD, CHOL, TG, and the correlation between the values and the negative correlation. -0.51, P0.001) analysis of the correlation between.IL-37 and IL-18: after Spearman correlation analysis, the serum IL-37 and IL-18 have positive correlation (r=0.21, P=0.04). Conclusion: IL-37 plasma level in ACS group is significantly higher than that in the stable group and the control group, and has a statistical difference (P0.05). Guan's inflammatory factors may become new inflammatory biomarkers in ACS patients.

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R541.4

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