内源性血管弹性蛋白酶在川崎病冠状动脉重构中的作用研究

The role of endogenous vascular elastase in coronary artery reconstruction in Kawasaki disease

摘要:

目的 探讨内源性血管弹性蛋白酶（EVE）对川崎病患儿冠状动脉重构的影响。方法 2012年1月至2013年4月诊断为川崎病的60例患儿作为病例组，分别于发病0~11 d（病理Ⅰ期）、发病12~25 d（病理Ⅱ期）抽取外周静脉血3 mL；60例同期因发热就诊的非川崎病患儿作为对照组，均于发热急性期空腹抽取外周静脉血3 mL。应用酶联免疫法（ELISA）检测各组血清中EVE、IL-6及血浆中血管内皮生长因子（VEGF）水平；病例组分别于发病的第一周末、第二周末和第四周末以超声心动图检查冠状动脉受损情况；Pearson相关分析评价EVE与IL-6和VEGF的相关性。结果 病例组Ⅰ期和Ⅱ期血清EVE和IL-6水平均明显高于对照组，而血浆VEGF水平均低于对照组（均P<0.05），且Ⅱ期EVE和IL-6水平均高于Ⅰ期（均P<0.05）；有冠状动脉损害的病理Ⅱ期患儿血清中EVE和IL-6的含量均显著高于无冠状动脉损害组，而血浆VEGF水平低于无冠状动脉损害组（均P<0.05）；有冠状动脉瘤的病理Ⅱ期患儿血清中EVE和IL-6的含量均显著高于无冠状动脉瘤组，而血浆VEGF水平低于无冠状动脉瘤组（均P<0.05）；EVE含量与IL-6水平呈正相关，而与VEGF水平呈负相关（分别r=0.915、-0.769，均P<0.05）。结论 EVE可能参与川崎病患儿冠状动脉重构，干预其活性可能缓解和阻止冠状动脉损害。

Abstract:

Objective To investigate the role of endogenous vascular elastase (EVE) in coronary artery between reconstruction among pediatric patients with Kawasaki disease (KD). Methods Sixty children who were diagnosed with KD between January 2012 and April 2013 were selected as the case group, and peripheral venous blood samples were collected on days 0-11 (pathological stage I) and days 12-25 (pathological stage Ⅱ) after the onset of disease; another 60 children without KD who visited the hospital due to acute fever during the same period were selected as the control group, and fasting peripheral venous blood samples were collected in the acute stage of fever. For both groups, serum levels of EVE and interleukin-6 (IL-6) and plasma vascular endothelial growth factor (VEGF) level were measured by enzyme-linked immunosorbent assay. For the case group, ultrasonic cardiography was used to detect coronary artery lesions (CALs) at the first, second and fourth weekends. The correlations of EVE level with IL-6 and VEGF levels were evaluated by Pearson correlation analysis. Results Serum levels of EVE and IL-6 in the case group in pathological stages I and Ⅱ were significantly higher than in the control group (P<0.05), but plasma VEGF levels in stages I and Ⅱ were significantly lower than in the control group (P<0.05); in the case group, EVE and IL-6 levels were significantly higher in stage Ⅱ than in stage I (P<0.05). In pathological stage Ⅱ, KD patients with CALs had significantly higher serum levels of EVE and IL-6 but significantly lower plasma VEGF levels compared with those without CALs (P<0.05); KD patients with coronary artery aneurysms (CAAs) had significantly higher serum levels of EVE and IL-6 but significantly lower plasma VEGF level compared with those without CAAs (P<0.05 for all). EVE level was positively correlated with IL-6 level (r=0.915, P<0.05), yet negatively correlated with VEGF level (r=-0.769, P<0.05). Conclusions EVE may participate in coronary artery reconstruction in children with KD. To interfere EVE activity may reduce and prevent CALs.