中性粒细胞激活在冠状动脉扩张发病机制中的作用研究

发布时间：2019-05-16 08:51

【摘要】：背景与目的冠脉扩张是一种以冠状动脉管腔异常扩大为表现的疾病。中性粒细胞激活可能参与到冠脉扩张的发病机制中。中性粒细胞激活后会释放胞内颗粒,包括蛋白酶、髓过氧化物酶等蛋白。目前研究已发现冠脉扩张患者中血浆中性粒细胞来源的丝氨酸蛋白酶水平升高,会破坏血管壁并导致冠脉扩张。目前中性粒细胞常用的激活标志有胞内髓过氧化物酶指数(MPXI)降低和血浆髓过氧化物酶(MPO)含量升高。中性粒细胞胞外捕获网(NETs)是中性粒细胞脱颗粒后的残骸。本研究的目的一是探究冠脉扩张患者外周血中性粒细胞是否存在激活现象。目的二是研究激活现象的病因。目的三是探索中性粒细胞胞外捕获网与冠脉扩张的关系。方法本研究使用行冠脉造影的受试者的外周血样本作为研究对象。第一部分纳入了61位冠脉扩张患者,82位冠脉狭窄患者以及75位冠脉正常患者。第二及第三部分纳入了冠脉扩张患者、冠脉狭窄患者以及冠脉正常患者各30位。使用流式细胞化学血细胞计数仪(ADVIA2120)分析胞内髓过氧化物酶指数(MPXI)。使用酶联免疫吸附法(ELISA)测定血浆髓过氧化物酶浓度。在部分二和三中使用ELISA法测定受试者血浆黏附分子、抗体滴度、炎症介质、分泌性白细胞蛋白酶抑制剂(SLPI)和NETs含量。此外还使用PicoGreen试剂测定dsDNA含量,以定量反映NETs浓度。结果冠脉扩张患者中MPXI降低,血浆MPO含量升高。MPXI与MPO成负相关关系。此外冠脉扩张患者血浆黏附分子浓度升高,白细胞介素1β可能是中性粒细胞激活的原因。冠脉扩张患者中NETs含量升高。结论本研究首次同时使用胞内外髓过氧化物酶含量检测法证明冠脉扩张患者外周血中性粒细胞存在广泛激活。冠脉扩张患者外周血中性粒细胞发生激活,释放胞内颗粒并生成NETs,加重血管壁的降解。中性粒细胞激活的原因可能是白细胞介素1β水平升高。
[Abstract]:Background and target coronary dilation is a disease characterized by an abnormal enlargement of the coronary lumen. Neutrophil activation may be involved in the pathogenesis of coronary dilation. Neutrophil activation will release the intracellular particles, including proteins such as proteases, myeloperoxidase, and the like. At present, it has been found that the increase in the level of the serine protease from the plasma neutrophils in patients with coronary dilation will destroy the vessel wall and cause coronary expansion. At present, the activation marker commonly used in neutrophils has an intracellular myeloperoxidase index (MPXI) and an increase in plasma myeloperoxidase (MPO) content. Neutrophil extracellular trap (NETs) is the remains of the neutrophils. The purpose of this study is to investigate the presence or absence of activation in the peripheral blood of patients with coronary expansion. Objective To study the causes of activation. Objective: To explore the relationship between the extracellular capture network of the neutrophils and the expansion of the coronary artery. Methods The peripheral blood samples from subjects who underwent coronary angiography were used as the subject of study. The first part included 61 patients with coronary dilation,82 patients with coronary stenosis and 75 patients with normal coronary artery disease. The second and third part included 30 patients with coronary artery expansion, patients with coronary artery stenosis and normal coronary artery. The intracellular myeloperoxidase index (MPXI) was analyzed using a flow cytometry (ADVA2120). Plasma myeloperoxidase concentration was determined using an enzyme-linked immunosorbent assay (ELISA). The plasma adhesion molecules, antibody titres, inflammatory mediators, secretory leukocyte protease inhibitors (SLPI) and NETs content in subjects were determined in part two and three using an ELISA method. The dsDNA content was also determined using the PicoGreen reagent to quantify the concentration of the NETs. Results In the patients with coronary dilation, MPXI decreased and the plasma MPO content increased. MPXI was negatively related to MPO. In addition, the plasma adhesion molecule concentration in the patients with coronary dilation was increased, and the interleukin-1 level could be the cause of the activation of the neutrophils. The contents of NEs in patients with coronary dilatation increased. Conclusion The first time in this study, the internal and external myeloperoxidase content detection method has been used to prove that the presence of neutrophils in the peripheral blood of patients with coronary expansion has been widely activated. Activation of peripheral blood neutrophils in patients with coronary dilation, release of intracellular particles and the formation of NEs, aggravate the degradation of the vessel wall. The cause of neutrophil activation may be an increase in the level of interleukin1.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R543.3

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