川崎病患儿外周血基质金属蛋白酶1的表达及其与冠状动脉损伤的关系

Matrix metalloproteinase-1 expression in the circulation of patients with Kawasaki disease and its role in the pathogenesis of coronary artery lesions

目的观察基质金属蛋白酶1(matrixmetalloproteinase1,MMP1)在川崎病患儿外周血不同时期的表达水平,探讨其在冠状动脉(简称冠脉)损伤中的作用。方法40例川崎病患儿(无冠脉损伤组23例,冠脉损伤组17例),按病程分为急性期、亚急性期和恢复期;另分别以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。应用酶联免疫吸附法检测血清MMP1蛋白水平、逆转录聚合酶链反应(RTPCR)检测外周血白细胞MMP1mRNA表达水平。结果急性期有、无冠脉损伤组血清MMP1和白细胞表达MMP1mRNA水平均明显高于发热对照组和正常对照组(均P<0.01),且冠脉损伤组MMP1蛋白和mRNA水平较无冠脉损伤组升高更为显著(P<0.05);到亚急性期、恢复期时MMP1蛋白和mRNA水平依次明显降低(各期间比较,均P<0.01)。川崎病组急性期血清MMP1蛋白水平与外周血白细胞计数呈显著正相关(r=0.750,P<0.01)。结论MMP1在川崎病急性期,尤其在冠脉损伤时表达明显升高;MMP1的过度表达可能与川崎病冠脉损伤的形成有关。

Objective Kawasaki disease （KD） is an acute and self-limited systemic vasculitis syndrome of unknown origin that mainly affects small and medium-sized arteries, particularly the coronary arteries, which is followed by aneurysm formation. Increased levels of matrix metalloproteinase-1 （ MMP-1 ）have been detected in aortic aneurysms in adults, suggesting an important role of MMP-1 in arterial wall destruction and resultant aneurysm formation. The aim of this study was to investigate the potential role of MMP-1 in the pathogenesis of coronary artery lesions in patients with KD. Methods Forty patients with KD, including 23 patients without coronary artery lesions （CAL） and 17 patients with CAL, as well as agematched 10 febrile and 10 healthy afebrile controls were studied. The duration of KD was divided into three phases： the acute phase, the subacute phase and the convalescent phase. Enzyme-linked immunosorbent assay was used to detect the protein levels of MMP-1 in the sera. MMP-1 mRNA expression in the circulating leucocytes was studied using reverse transcription-polymerase chain reaction. Results Levels of MMP-1 protein in serum and MMP-1 mRNA expression in the leucocytes were significantly elevated at the acute phase in the two groups of KD patients（CAL group：14. 91 ±3.88 ng/ml and 0. 89 ±0. 15 ng/ml; NO-CAL group：ll. 27 ±3.28 ng/ml and 0. 77 ±0. 14,respectively） , compared with febrile （7.05 ± 1.98 ng/ml and 0.45 ± 0. 12 ng/ml, respectively） and afebrile（ 5. 13 ± 1.20 ng/ml and 0. 29 ± 0. 12 ng/ml, respectively）controls （P 〈0. 01）. Furthermore, MMP-1 protein and MMP-1 mRNA levels were significantly higher in KD patients with CAL than in KD patients without CAL （ P 〈 0. 05 ）. There was a significantly positive correlation between the serum protein level of MMP-1 at the acute phase of KD and the circulating leucocytes counts （r = 0. 750, P 〈0.01 ）. The MMP-1 serum protein level and mRNA expression in the leucocytes at the acute phase of the two KD groups decreased obviously from the subacute through the convalescent phases（ P 〈 0. 05 or P 〈 0. 01 ）. Conclusion The expression of MMP-1 at the acute phase of KD was significantly elevated, especially in KD patients with CAL. MMP-1 might be involved in the formation of coronary artery lesions and pathogenesis of KD.