急性心肌梗死患者血清IL-18升高参与斑块破裂的机制

Increasing Level of Serum IL-18 in Patients with Acute Myocardial Infarction Participates in the Mechanism of Plaque Rupture

目的观察急性心肌梗死患者血清白细胞介素18(IL-18)的水平,探讨其导致动脉粥样斑块破裂的可能机制。方法采用ELISA分别检测急性心肌梗死组(n=20)、稳定型心绞痛组(n=20)和正常对照组(n=20)中血清IL-18和基质金属蛋白酶9(MMP-9)水平,用流式细胞术检测各组外周血单核细胞表面细胞外基质金属蛋白酶诱导因子(EMMPRIN)的表达;在体外,分别通过实时定量聚合酶链反应和蛋白印迹法检测IL-18对人外周血单核细胞EMMPRIN mRNA和蛋白表达的影响。结果急性心肌梗死组血清IL-18、MMP-9水平和外周血单核细胞表达的EMMPRIN均明显高于稳定型心绞痛组和正常对照组,且急性心肌梗死组患者血清IL-18水平与外周血单核细胞表达的EMMPRIN呈正相关(r2=0.57,P<0.001)。在体外,IL-18能刺激外周血单核细胞EMMPRIN表达上调(P<0.05)。结论 IL-18能够上调单核细胞EMMPRIN的表达,可能通过这一机制刺激MMP-9分泌,降低动脉粥样硬化斑块的稳定性,引起斑块破裂。

Aim To study the effect of serum interleukin-18（IL-18） in human acute myocardial infarction and its possible mechanism in the process of plaque rupture. Methods Serum levels of IL-18 and MMP-9 proteins were determined using commercially available enzyme-linked immunoassays in each group： acute myocardial infarction（AMI） group,stable angina pectoris（SAP） group and heathy control group（n = 20,respectively）. Flow cytometry was applied to assess extracellular matrix metalloproteinase inducer（EMMPRIN） expression on the surface of monocytes of each group. In vitro experiment,quantitative real-time polymerase chain reaction（QRT-PCR） and Western blot were performed to compare EMMPRIN expression of monocytes cultured in presence and absence of IL-18. Results In patients with AMI,serum level of IL-18 and MMP-9 and expression of EMMPRIN on monocytes markedly increased compared with patiens with SAP and heathy control group. Furthermore,increased level of IL-18 was positively associated with elevated expression of EMMPRIN on monocytes in AMI group（r2= 0. 57,P 〈 0. 001）. The data proved that expression of EMMPRIN was enhanced in monocytes cultured in presence of IL-18（P 〈 0. 05）. Conclusion IL-18 stimulates monocytes to express EMMPRIN,which may induce secretion of MMP-9,contributing to atherosclerotic plaque instability and rupture.