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秋水仙碱对心肌梗死后 MMP-9、NOX2 和 TGF-β1 的影响。

Effect of Colchicine in reducing MMP-9, NOX2, and TGF- β1 after myocardial infarction.

机构信息

Doctoral Program of Medical Science, Brawijaya University, Malang, East Java, Indonesia.

Department of Cardiology and Vascular Medicine, Faculty of Medicine, Jember University, Jember, East Java, Indonesia.

出版信息

BMC Cardiovasc Disord. 2023 Sep 11;23(1):449. doi: 10.1186/s12872-023-03464-9.

Abstract

BACKGROUND

According to WHO 2020, CAD is the second leading cause of death in Indonesia with death cases reaching 259,297 or 15.33% of total deaths. Unfortunately, most of the patients of CAD in Indonesia did not match the golden period or decline to be treated with Percutaneous Coronary Intervention (PCI). Based on the recent study, there were increases in MMP-9, NOX2, and TGF-β1 in STEMI patients which contribute to cardiac remodeling. Moreover, there is controversy regarding the benefit of late PCI (12-48 hours after onset of STEMI) in stable patients. Lately, colchicine is widely used in cardiovascular disease. This study was conducted to explore the effect of colchicine to reduce MMP- 9, NOX2, and TGF-β1 levels after myocardial infarction in stable patients.

METHOD

In this clinical trial study, we assessed 129 STEMI patients, about 102 patients who met inclusion criteria were randomized into four groups. Around 25 patients received late PCI (12-48 h after the onset of chest pain), optimal medical treatment (OMT) for STEMI, and colchicine; 24 patients received late PCI and OMT; 22 patients didn't get the revascularization (No Revas), OMT, and colchicine; and 31 patients received No Revas and OMT only. The laboratory test for MMP-9, NOX2, and TGF-β1 were tested in Day-1 and Day-5. The data were analyzed using Mann-Whitney.

RESULTS

A total of 102 patients with mean age of 56 ± 9.9, were assigned into four groups. The data analysis showed significant results within No Revas + OMT + Colchicine group versus No Revas + OMT + Placebo in MMP-9 (Day-1: p = 0.001; Day-5: p = 0.022), NOX2 (Day-1: p = 0.02; Day-5: p = 0.026), and TGF-β1 (Day-1: p = 0.00; Day-5: p = 0.00) with the less three markers in OMT + Colchicine group than OMT + Placebo group. There were no significant differences within the late PCI + OMT + colchicine group and PCI + OMT + Placebo group.

CONCLUSIONS

Colchicine could significantly reduce MMP-9, NOX2, and TGF-β1 levels in stable STEMI patients. So that, colchicine could be a potential agent in STEMI patients and prevent cardiac remodeling events.

摘要

背景

根据世界卫生组织 2020 年的数据,CAD 是印度尼西亚的第二大死因,死亡病例达 259297 例,占总死亡人数的 15.33%。不幸的是,印度尼西亚的大多数 CAD 患者不符合经皮冠状动脉介入治疗 (PCI) 的黄金时期或下降期。根据最近的研究,STEMI 患者的 MMP-9、NOX2 和 TGF-β1 增加,导致心脏重构。此外,对于稳定型患者,晚期 PCI(STEMI 发作后 12-48 小时)的益处存在争议。最近,秋水仙碱在心血管疾病中得到了广泛应用。本研究旨在探讨秋水仙碱对稳定型 STEMI 患者心肌梗死后降低 MMP-9、NOX2 和 TGF-β1 水平的作用。

方法

在这项临床试验研究中,我们评估了 129 例 STEMI 患者,约有 102 例符合纳入标准的患者被随机分为四组。约 25 例患者接受晚期 PCI(胸痛发作后 12-48 小时)、STEMI 的最佳药物治疗 (OMT) 和秋水仙碱;24 例患者接受晚期 PCI 和 OMT;22 例未进行血运重建(No Revas)、OMT 和秋水仙碱;31 例患者仅接受 No Revas 和 OMT。在第 1 天和第 5 天检测 MMP-9、NOX2 和 TGF-β1 的实验室检查。数据采用 Mann-Whitney 分析。

结果

共纳入 102 例平均年龄 56±9.9 岁的患者,分为四组。数据分析显示,No Revas+OMT+Colchicine 组与 No Revas+OMT+Placebo 组之间 MMP-9(第 1 天:p=0.001;第 5 天:p=0.022)、NOX2(第 1 天:p=0.02;第 5 天:p=0.026)和 TGF-β1(第 1 天:p=0.00;第 5 天:p=0.00)的差异有统计学意义,并且 OMT+Colchicine 组三个标志物的水平均低于 OMT+Placebo 组。晚期 PCI+OMT+Colchicine 组与 PCI+OMT+Placebo 组之间无显著差异。

结论

秋水仙碱可显著降低稳定型 STEMI 患者 MMP-9、NOX2 和 TGF-β1 水平。因此,秋水仙碱可能是 STEMI 患者的潜在治疗药物,可预防心脏重构事件。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9016/10496361/5ea03b192c5b/12872_2023_3464_Fig1_HTML.jpg

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