川崎病患儿冠状动脉损害相关因素临床研究
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摘要
川崎病(kawasaki disease,KD)是以全身性血管炎为主要病变的急性、发热性、出疹性疾病。近年来全球发病率有逐年上升的趋势。该病主要累及中小血管,特别是冠状动脉损害是该病的主要危害,部分患儿可在急性期或以后形成冠状动脉扩张、冠状动脉瘤和多发性狭窄,严重威胁患儿的生活质量甚至生命安全,是儿童后天获得性心脏病的重要原因之一。所以早期诊断KD的心肌及冠脉损害以便及早用药及预防并发症有着重大的临床意义。但本病发病机制不十分清楚,但目前多认为KD是一种由多种感染性病原触发的免疫系统异常激活引起的血管炎。现有研究表明川崎病发病过程中存在着明显抗β2GPI抗体及基质金属蛋白酶9(MMP-9)增高,且二者在川崎病发生、发展及进展至合并冠状动脉损害的过程中,与其有密切关系。
本研究内容包括:(1)采用ELISA方法检测KD患儿急性期与发热对照组血清抗β2GPI抗体及基质金属蛋白酶9(MMP-9)的水平并进行比较。(2)就KD患儿急性期血清抗β2GPI抗体及基质金属蛋白酶9(MMP-9)升高和冠脉扩张之间的关系进行初步研究。(3)对KD急性期患儿血清抗β2GPI抗体及基质金属蛋白酶9(MMP-9)升高之间的关系及其与冠脉扩张的关系进行初步研究。
结果表明:KD患儿急性期血清抗β2GPI抗体及基质金属蛋白酶9(MMP-9)的水平明显高于发热对照组,经统计学分析有显著意义,有可能成为早期诊断川崎病血清学指标,同时二者在川崎病发病过程中可能有协同作用。本研究还显示抗β2GPI抗体及MMP-9在川崎病急性期尤其伴冠状动脉病变时明显升高,二者可能均参与了川崎病血管炎尤其是冠脉损伤扩张的病理过程,提示抗β2GPI抗体及MMP-9与KD有很强的相关性,可能成为KD冠状动脉损伤的标志性指标。这对早期诊断川崎病及预测合并冠脉病变具有重要的理论与临床意义,可以用来指导临床早期用药,并对预后判断具有重要参考价值。
Objective: Kawasaki disease (kawasaki disease, KD) is systemic vasculitis of the main acute lesions, fever, rash disease. In recent years, with the progress of technology and scientific development, as well as clinicians to raise awareness of the disease, the global incidence rate has increased year by year trends. The disease mainly involving small blood vessels, in particular Coronary artery disease is the damage to the main hazards, and some children in the acute phase or after the formation of coronary artery dilatation, coronary artery aneurysms and multiple narrow, serious threat to the quality of life for children with life or safety of the children acquired heart disease One of the important factors. However, the pathogenesis of this disease is not very clear, but more than that KD is a variety of sexually transmitted infections from the original trigger abnormal activation of the immune system caused by vasculitis that systemic immune activation, and increased cytokine production of autoantibodies increase is the KD characteristics. KD plasma in the presence of circulating antibody, such as cytoplasmic antibodies, anti-endothelial cell antibodies, anticardiolipin antibody, their IL-1β, TNFαor IFN-γstimulated endothelial cells with cytotoxic effect However, their specificity still controversial, and the vascular injury may occur process.Β2GPI is a relatively rich plasma glycoprotein is to determine the ACA and cardiac combination of phospholipid cofactor, in some autoimmune diseases is an important autoantigen, immune activation in endothelial cells, vascular inflammation and thrombosis formation process from the role of crucial importance, especially anti-β2GP1 the emergence of antibodies increased the risk of thrombosis. At the same time a specific collagenase and elastase activity in the zinc-dependent matrix metalloproteinase superfamily of MMP-9, can degrade collagen from the main organization, flexible hardware protein, a protein vascular endothelial polysaccharide lower in inflammation in response to inflammatory cells such as T-lymphocytes, monocytes macrophages to the vascular wall deep Mobile, immune injury to the blood vessel wall deep development. MMP-9 through the degradation of extracellular matrix, in atherosclerotic vascular remodeling and plaque instability caused by cardiovascular diseases in the development process plays an important role. Some scholars study the use of high-fat meal-induced rabbit model of atherosclerosis found in atherosclerosis and progress with the process of activation of MMPs, and gradually increasing trend. In recent years, studies indicate that the pathogenesis of Kawasaki disease there is a clear anti-β2GPI antibody and matrix metalloproteinase-9 (MMP-9) increased, and two in Kawasaki disease, development and progress of coronary artery damage to the merger process, which they have close relationship. This study aimed to investigate the acute phase of Kawasaki disease in children with serum anti-β2 GPI antibody, MMP-9 levels of Kawasaki disease in the early diagnosis and prediction of the value of coronary artery disease.
Methods: First Clinical Hospital of Jilin University Pediatric clear diagnosis of KD 37 cases of children hospitalized for observation group, which Doppler ultrasound examination of 20 cases with normal coronary artery, the merger were 17 cases of coronary artery disease. Replacement of 20 cases in our hospital during the same period in the age of diagnosis was similar to sepsis or pneumonia and other infectious diseases in children with fever control group, all except for the heart, liver, kidney, blood diseases and autoimmune diseases such as rheumatoid. By ELISA measurement of serum antibody anti-β2GPI, MMP-9 levels. Using SAS software analysis of the data collected, testedα= 0.05 level.
Results: Observer Group in children with Kawasaki disease and fever in the control group, serum anti-β2GPIantibody levels are 8.0595±1.9177U/ml and 5.21±1.1259U/ml; serum levels of MMP-9 is 912.73 and 790±87.396ng/ml 14.712ng/ml, the two were significantly different, the statistical test statistically significant (P<0.05); Observer Group coronary artery and coronary artery injury group were normal serum level of anti-β2GPI serum antibody levels are 9.3118±2.1482 U/ml and 6.995±0.697U/ml, serum levels of MMP-9 is 979.71±90.559ng/ml and 855.8±11.87ng/ml, the two were significantly different statistically the test statistical significance (P<0.05) in children with Kawasaki disease observed in the serum MMP-9, anti-β2GP1antibody levels were significantly correlated with a correlation coefficient r=0.66533, (P<0.0001).
Conclusion: Anti-β2GPI antibody and MMP-9 in the acute phase of Kawasaki disease with coronary artery disease, particularly significantly increased, and they may be involved in the Kawasaki disease are especially coronary vasculitis injury expansion of the pathologic process, suggesting that anti-β2GPI antibody and MMP﹣9 and KD have a strong correlation, the early diagnosis of Kawasaki disease may become serological indicators, in particular, may be a sign of coronary artery lesions KD indicators at the same time both in Kawasaki disease may occur in the process of the development of synergies. This early diagnosis and prediction of the merger of Kawasaki disease and coronary artery disease early clinical drug guide has important theoretical and clinical significance.
本研究内容包括:(1)采用ELISA方法检测KD患儿急性期与发热对照组血清抗β2GPI抗体及基质金属蛋白酶9(MMP-9)的水平并进行比较。(2)就KD患儿急性期血清抗β2GPI抗体及基质金属蛋白酶9(MMP-9)升高和冠脉扩张之间的关系进行初步研究。(3)对KD急性期患儿血清抗β2GPI抗体及基质金属蛋白酶9(MMP-9)升高之间的关系及其与冠脉扩张的关系进行初步研究。
结果表明:KD患儿急性期血清抗β2GPI抗体及基质金属蛋白酶9(MMP-9)的水平明显高于发热对照组,经统计学分析有显著意义,有可能成为早期诊断川崎病血清学指标,同时二者在川崎病发病过程中可能有协同作用。本研究还显示抗β2GPI抗体及MMP-9在川崎病急性期尤其伴冠状动脉病变时明显升高,二者可能均参与了川崎病血管炎尤其是冠脉损伤扩张的病理过程,提示抗β2GPI抗体及MMP-9与KD有很强的相关性,可能成为KD冠状动脉损伤的标志性指标。这对早期诊断川崎病及预测合并冠脉病变具有重要的理论与临床意义,可以用来指导临床早期用药,并对预后判断具有重要参考价值。
Objective: Kawasaki disease (kawasaki disease, KD) is systemic vasculitis of the main acute lesions, fever, rash disease. In recent years, with the progress of technology and scientific development, as well as clinicians to raise awareness of the disease, the global incidence rate has increased year by year trends. The disease mainly involving small blood vessels, in particular Coronary artery disease is the damage to the main hazards, and some children in the acute phase or after the formation of coronary artery dilatation, coronary artery aneurysms and multiple narrow, serious threat to the quality of life for children with life or safety of the children acquired heart disease One of the important factors. However, the pathogenesis of this disease is not very clear, but more than that KD is a variety of sexually transmitted infections from the original trigger abnormal activation of the immune system caused by vasculitis that systemic immune activation, and increased cytokine production of autoantibodies increase is the KD characteristics. KD plasma in the presence of circulating antibody, such as cytoplasmic antibodies, anti-endothelial cell antibodies, anticardiolipin antibody, their IL-1β, TNFαor IFN-γstimulated endothelial cells with cytotoxic effect However, their specificity still controversial, and the vascular injury may occur process.Β2GPI is a relatively rich plasma glycoprotein is to determine the ACA and cardiac combination of phospholipid cofactor, in some autoimmune diseases is an important autoantigen, immune activation in endothelial cells, vascular inflammation and thrombosis formation process from the role of crucial importance, especially anti-β2GP1 the emergence of antibodies increased the risk of thrombosis. At the same time a specific collagenase and elastase activity in the zinc-dependent matrix metalloproteinase superfamily of MMP-9, can degrade collagen from the main organization, flexible hardware protein, a protein vascular endothelial polysaccharide lower in inflammation in response to inflammatory cells such as T-lymphocytes, monocytes macrophages to the vascular wall deep Mobile, immune injury to the blood vessel wall deep development. MMP-9 through the degradation of extracellular matrix, in atherosclerotic vascular remodeling and plaque instability caused by cardiovascular diseases in the development process plays an important role. Some scholars study the use of high-fat meal-induced rabbit model of atherosclerosis found in atherosclerosis and progress with the process of activation of MMPs, and gradually increasing trend. In recent years, studies indicate that the pathogenesis of Kawasaki disease there is a clear anti-β2GPI antibody and matrix metalloproteinase-9 (MMP-9) increased, and two in Kawasaki disease, development and progress of coronary artery damage to the merger process, which they have close relationship. This study aimed to investigate the acute phase of Kawasaki disease in children with serum anti-β2 GPI antibody, MMP-9 levels of Kawasaki disease in the early diagnosis and prediction of the value of coronary artery disease.
Methods: First Clinical Hospital of Jilin University Pediatric clear diagnosis of KD 37 cases of children hospitalized for observation group, which Doppler ultrasound examination of 20 cases with normal coronary artery, the merger were 17 cases of coronary artery disease. Replacement of 20 cases in our hospital during the same period in the age of diagnosis was similar to sepsis or pneumonia and other infectious diseases in children with fever control group, all except for the heart, liver, kidney, blood diseases and autoimmune diseases such as rheumatoid. By ELISA measurement of serum antibody anti-β2GPI, MMP-9 levels. Using SAS software analysis of the data collected, testedα= 0.05 level.
Results: Observer Group in children with Kawasaki disease and fever in the control group, serum anti-β2GPIantibody levels are 8.0595±1.9177U/ml and 5.21±1.1259U/ml; serum levels of MMP-9 is 912.73 and 790±87.396ng/ml 14.712ng/ml, the two were significantly different, the statistical test statistically significant (P<0.05); Observer Group coronary artery and coronary artery injury group were normal serum level of anti-β2GPI serum antibody levels are 9.3118±2.1482 U/ml and 6.995±0.697U/ml, serum levels of MMP-9 is 979.71±90.559ng/ml and 855.8±11.87ng/ml, the two were significantly different statistically the test statistical significance (P<0.05) in children with Kawasaki disease observed in the serum MMP-9, anti-β2GP1antibody levels were significantly correlated with a correlation coefficient r=0.66533, (P<0.0001).
Conclusion: Anti-β2GPI antibody and MMP-9 in the acute phase of Kawasaki disease with coronary artery disease, particularly significantly increased, and they may be involved in the Kawasaki disease are especially coronary vasculitis injury expansion of the pathologic process, suggesting that anti-β2GPI antibody and MMP﹣9 and KD have a strong correlation, the early diagnosis of Kawasaki disease may become serological indicators, in particular, may be a sign of coronary artery lesions KD indicators at the same time both in Kawasaki disease may occur in the process of the development of synergies. This early diagnosis and prediction of the merger of Kawasaki disease and coronary artery disease early clinical drug guide has important theoretical and clinical significance.
引文
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