中性粒細(xì)胞激活在冠狀動脈擴(kuò)張發(fā)病機(jī)制中的作用研究
發(fā)布時間：2019-05-16 08:51
【摘要】：背景與目的冠脈擴(kuò)張是一種以冠狀動脈管腔異常擴(kuò)大為表現(xiàn)的疾病。中性粒細(xì)胞激活可能參與到冠脈擴(kuò)張的發(fā)病機(jī)制中。中性粒細(xì)胞激活后會釋放胞內(nèi)顆粒,包括蛋白酶、髓過氧化物酶等蛋白。目前研究已發(fā)現(xiàn)冠脈擴(kuò)張患者中血漿中性粒細(xì)胞來源的絲氨酸蛋白酶水平升高,會破壞血管壁并導(dǎo)致冠脈擴(kuò)張。目前中性粒細(xì)胞常用的激活標(biāo)志有胞內(nèi)髓過氧化物酶指數(shù)(MPXI)降低和血漿髓過氧化物酶(MPO)含量升高。中性粒細(xì)胞胞外捕獲網(wǎng)(NETs)是中性粒細(xì)胞脫顆粒后的殘骸。本研究的目的一是探究冠脈擴(kuò)張患者外周血中性粒細(xì)胞是否存在激活現(xiàn)象。目的二是研究激活現(xiàn)象的病因。目的三是探索中性粒細(xì)胞胞外捕獲網(wǎng)與冠脈擴(kuò)張的關(guān)系。方法本研究使用行冠脈造影的受試者的外周血樣本作為研究對象。第一部分納入了61位冠脈擴(kuò)張患者,82位冠脈狹窄患者以及75位冠脈正�；颊摺５诙暗谌糠旨{入了冠脈擴(kuò)張患者、冠脈狹窄患者以及冠脈正�；颊吒�30位。使用流式細(xì)胞化學(xué)血細(xì)胞計數(shù)儀(ADVIA2120)分析胞內(nèi)髓過氧化物酶指數(shù)(MPXI)。使用酶聯(lián)免疫吸附法(ELISA)測定血漿髓過氧化物酶濃度。在部分二和三中使用ELISA法測定受試者血漿黏附分子、抗體滴度、炎癥介質(zhì)、分泌性白細(xì)胞蛋白酶抑制劑(SLPI)和NETs含量。此外還使用PicoGreen試劑測定dsDNA含量,以定量反映NETs濃度。結(jié)果冠脈擴(kuò)張患者中MPXI降低,血漿MPO含量升高。MPXI與MPO成負(fù)相關(guān)關(guān)系。此外冠脈擴(kuò)張患者血漿黏附分子濃度升高,白細(xì)胞介素1β可能是中性粒細(xì)胞激活的原因。冠脈擴(kuò)張患者中NETs含量升高。結(jié)論本研究首次同時使用胞內(nèi)外髓過氧化物酶含量檢測法證明冠脈擴(kuò)張患者外周血中性粒細(xì)胞存在廣泛激活。冠脈擴(kuò)張患者外周血中性粒細(xì)胞發(fā)生激活,釋放胞內(nèi)顆粒并生成NETs,加重血管壁的降解。中性粒細(xì)胞激活的原因可能是白細(xì)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.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R543.3
本文編號：2478168
[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.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R543.3
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