中性粒细胞相关蛋白酶减轻急性心肌梗死早期损伤的研究  

Knockout of neutrophil-associated protease reduces early myocardial injury in mice with acute myocardial infarction

作　　者：张颖函 乔博康 王媛[1] 王雪[1] 王贤德 杜杰[1] ZHANG Yinghan;QIAO Bokang;WANG Yuan;WANG Xue;WANG Xiande;DU Jjie(Department of Vascular Biology,Beijing Anzhen Hospital,Capital Medical University,Beijing Institute of Heart,Lung and Blood Vessel Diseases,Beijing 100029,China)

机构地区：[1]首都医科大学附属北京安贞医院-北京市心肺血管疾病研究所血管生物研究室,100029

出　　处：《心肺血管病杂志》2024年第2期201-206,共6页Journal of Cardiovascular and Pulmonary Diseases

基　　金：国家自然科学基金(82200459);科技部国家重点研发计划(2021YFA0805102)。

摘　　要：目的:明确中性粒细胞弹性蛋白酶及蛋白酶3(neutrophil elastase/proteinase 3, NE/PR3)在心肌梗死早期损伤阶段中的作用。方法:ELISA试剂盒检测急性心肌梗死患者及健康对照组外周血中NE/PR3含量;基于冠状动脉左前降支结扎术构建心肌梗死模型,通过WB及RT-QPCR检测心肌梗死后0、1、3、7d时心脏组织中NE/PR3的表达变化;小型动物心脏超声仪进行心功能检测、免疫组化染色以及Western blot检测纤维化相关蛋白(α-smooth muscle actin,α-SMA)变化明确敲除NE/PR3的影响。结果:心肌梗死患者外周血中NE/PR3含量以及中性粒细胞的占比均明显升高;在心肌梗死小鼠的心脏组织中表达量明显升高,且主要在梗死后1d时最为明显;NE/PR3基因缺失小鼠心肌梗死早期的纤维化程度增加、提高了心肌梗死后小鼠存活率、减少早期心脏破裂率并改善损伤早期心功能。结论:敲除中性粒细胞弹性蛋白酶NE/PR3可通过促进早期成纤维细胞活化转换为肌成纤维细胞促进心脏修复从而减少了早期心脏破裂等危险事件的发生及心脏损伤。Objective:To clarify the role of neutrophil elastase and proteinase 3(NE/PR3)in the early stages of myocardial infarction injury.Methods:ELISA kits were used to detect NE/PR3 levels in peripheral blood of patients with acute infarction and healthy controls;an infarction model was constructed based on coronary artery left anterior descending ligation,and the expression of NE/PR3 in cardiac tissues were detected at 0,1,3,and 7 days after the infarction by WB and RT-QPCR;the effects of knockdown of NE/PR3 were clarified by cardiac function tests performed by small-animal cardiac echocardiographs,immunohistochemical staining,and changes in fibrosis-associated protein(α-SMA)detected by Western blot.Results:The levels of NE/PR3 and the percentage of neutrophils in peripheral blood were significantly higher in patients with myocardial infarction;the expression was significantly higher in cardiac tissues of infarcted mice and was most pronounced mainly at 1 day post-infarction;and NE/PR3-deficient mice showed increased fibrosis in the early infarction period,improved survival in post-infarcted mice,reduced the rate of early cardiac rupture,and improved cardiac function in the early period of injury.Conclusions:Knockdown of neutrophil elastase NE/PR3 promotes cardiac repair by facilitating the conversion of fibroblasts to myofibroblasts thereby reducing theoccurrence of dangerous events such as early cardiac rupture and cardiac injury.

关 键 词：中性粒细胞蛋白酶 心肌梗死早期损伤 蛋白酶3 纤维化 

分 类 号：R54[医药卫生—心血管疾病]