川崎病患儿外周血基质金属蛋白酶-9的表达及其与冠状动脉损伤的关系(英文)

Matrix metalloproteinase29 expression in the peripheral blood of children with Kawasaki disease and its relationship with coronary artery lesions

摘要:

目的 观察MMP 9在川崎病 (KD)患儿不同时期表达水平 ,探讨其在冠状动脉损伤中的可能作用。方法 选择KD患儿 2 7例为研究对象 (无冠脉损伤组 10例 ,冠脉损伤组 17例 ) ,取年龄相仿的 10例败血症患儿、10例健康儿童为发热对照组和正常对照组。分别应用明胶酶谱法、酶联免疫吸附法检测血清MMP 9的活性和蛋白浓度 ,半定量RT PCR的方法检测外周血白细胞MMP 9mRNA表达水平。结果 (1)冠脉损伤组急性期血清MMP 9活性和蛋白水平 (10 .2± 2 .2 ,114 6± 6 91ng/ml)较无冠脉损伤组显著增高 (6 .2± 2 .1,4 5 7± 133ng/ml,P <0 .0 5 )。两组均较正常对照组 (0 .1± 0 .0 ,72± 2 4ng/ml)和发热对照组 (3.1± 1.4 ,2 2 1± 15 4ng/ml)显著增高 (P <0 .0 1或P <0 .0 5 )。 (2 )KD患儿急性期血清MMP 9蛋白水平与外周血白细胞计数显著正相关 (r =0 .4 80 ,P <0 .0 5 )。 (3)两组KD患儿急性期外周血白细胞MMP 9mRNA表达水平无显著性差异 ,但均显著高于发热对照组和正常对照组 (P <0 .0 1)。 (4)川崎病患儿急性期血清MMP 9活性、蛋白浓度和白细胞表达MMP 9mRNA水平 ,在亚急性期、恢复期均依次明显降低 (P <0 .0 1)。结论 MMP 9在川崎病患儿急性期 ,尤其在伴冠状动脉损伤时表达明显升高 ;MMP 9可能参与了川崎病冠状

Abstract:

Objective Matrix metalloproteinase-9 (MMP-9), a metalloproteinase, is capable of degrading type IV, V collagens, as well as gelatins. Increased levels of MMP-9 have been detected in aortic aneurysms in adult human, suggesting its role in arterial wall destruction and aneurysm formation. This study was designed to investigate the potential role of MMP-9 in the pathogenesis of coronary artery lesions in Kawasaki disease (KD) patients. Methods Twenty-seven children with KD [17 with coronary artery lesions (CALs) and 10 without] and age-matched 10 febrile and 10 healthy controls were enrolled in this study. Gelatin zymography and ELISA were used to detect the activity and levels of serum MMP-9. MMP-9 mRNA expression in the leucocytes was detected using reverse transcription-polymerase chain reaction (RT-PCR). Results 1) The activity ( 10.2± 2.2) and levels of MMP-9 (1 116 ±691 ng/ml) in KD patients with CALs in the acute phase were significantly higher than those without CALs ( 6.2± 2.1, 457±133 ng/ml, respectively; P< 0.05). Both of them in either the KD patients with CALs or without were higher than those of the healthy controls ( 0.1± 0.0, 72±24 ng/ml, respectively; P< 0.01) and the febrile controls ( 3.1± 1.4, 221±154 ng/ml, respectively; P< 0.05). 2) There was a significantly positive correlation between the serum MMP-9 protein levels and the circulating leucocytes counts in KD patients in the acute phase (r= 0.480, P< 0.05). 3) The MMP-9 mRNA expression in the leucocytes of KD patients in the acute phase were significantly elevated, as compared with the febrile and healthy controls (P< 0.01). There were no significant differences in the MMP-9 mRNA expressions between the two KD groups. 4) The activity, protein levels and mRNA expression of MMP-9 in the KD patients decreased obviously from the subacute through the convalescent phases, as compared with the acute phase (P< 0.01). Conclusions The MMP-9 expression in KD patients in the acute phase was significantly elevated, especially in those with CALs. MMP-9 may be involved in the development of coronary artery lesions in KD.