社会快速发展所导致的饮食结构改变使得心血管疾病（Cardiovascular disease, CVD）的发生率逐年升高，其中急性心肌梗死（Acute myocardial infarction, AMI）发病快，死亡率高，极大地加重了中国社会的疾病负担，虽然随着心血管 介入技术的应用和普及，急性心肌梗死（Acute myocardial infarction, AMI）尤其是ST段抬高型心肌梗死（ST-elevation myocardial infarction, STEMI）患者的短期和长期预后都得到了很大程度的改善，但是冠脉介入诊疗技术（Percutaneous coronary intervention, PCI）的应用也并不能完全预防ST段抬高型心肌梗死后机 械并发症（Post-infarction mechanical complication）的发生与发展。相较于急性心肌梗死后心力衰竭和恶性心律失常，心肌梗死后机械并发症虽然发生率较低，但是死亡率极高，尤其左心室游离壁破裂（Post-infarction cardiac rupture）最为凶险，一旦发生病情进展迅速，死亡率接近100%，目前虽然有报道可以通过外科手术技术利用手术胶或者有胶原纤维的补片进行心肌破口的封堵，但是仍有35%以上的术后患者在院内死亡，因此提高对此类心梗后并发症的预防有着十分重要的临床价值。本研究论文致力于提供一种具有临床转化前景的预防心梗后心脏破裂的药物干预方式，并阐述其主要的作用机制和细胞靶点，为之后可能的临 床试验提供科学依据。

心肌梗死后机械并发症根据心肌撕裂的部位分为室间隔穿孔，乳头肌断裂和心脏破裂，是急性心肌梗死最危险严重的并发症。急性心肌梗死发生后，心肌损伤和修复机制迅速启动，缺血梗死区心肌由于缺血缺氧发生坏死和崩解，心肌组织损伤释放出的趋化因子入血激活并募集炎症免疫细胞，炎症细胞识别并粘附到受损内皮，随后穿越心肌微血管内皮屏障，进入心肌细胞间质吞噬坏死和凋亡细 胞并分泌细胞因子对细胞外基质进行重塑，同时负责修复心肌的心肌成纤维细胞也向梗死区和周边区趋化迁移进入梗死区，经过细胞因子，如转化生长因子β刺激后，心肌成纤维细胞功能活化转化为肌成纤维细胞，大量分泌各种胶原纤维，粘多糖重建细胞外基质并进行心肌组织修复。急性心肌梗死后心肌损伤过重或者 心肌修复不足易导致心脏破裂的发生和进展。

巨噬细胞参与多种组织器官功能的损伤和修复，在急性心肌梗死后早期有大量巨噬细胞渗入心肌组织间隙并向M1极化，M1型巨噬细胞可通过多种途径加 重急性心肌梗死后心肌损伤造成心脏破裂的发生。一方面，M1型巨噬细胞功能激活后分泌多种炎症因子，其中主要包括白细胞介素家族和肿瘤坏死因子家族炎症因子，心肌微环境中的过度炎症因子释放作用于梗死区以及周边区心肌细胞、内皮细胞和心肌成纤维细胞之后，可以通过结合作用于这些靶细胞表面的受体激活下游通路导致细胞坏死或者凋亡，释放氧自由基促进梗死心肌组织细胞脂质过氧化；同时心血管疾病可以引起全身系统性脂质过氧化和氧化应激水平升高，主要表现为血浆中代谢产物甘油磷脂（glycerophospholipid, GPL）、氧化磷脂（oxidized phospholipid, oxPL）和衍生自多不饱和脂肪酸（polyunsaturated fatty acids, PUFAs）的下游代谢物，例如花生四烯酸和亚油酸显著升高，心肌微环境 和全身系统性的脂质过氧化可诱发梗死及周边区心肌组织中有利于心肌修复的 细胞，如心肌成纤维细胞的铁死亡，阻碍心肌修复，加重心脏破裂的风险。另一方面，心肌梗死后炎症因子上调和 ROS 激活可以促进成熟的巨噬细胞向促炎巨 噬细胞方向极化，在此过程中，经典炎症激活途径NF-κB和非经典途径C/EBPβ被激活后协同上调金属基质蛋白酶家族基因转录和表达，导致细胞外基质过度分解和流失，加重心肌损伤，增加心梗后机械并发症的发生风险。

本研究论文致力于研究证明一种药物组合（中药通心络，负荷量他汀和尼可地尔）具有显著的预防心肌梗死后心脏破裂作用，并阐述其主要通过抑制巨噬细胞极化介导的细胞外基质过度分解和心肌成纤维细胞铁死亡，发挥改善心肌损伤 促进心肌修复作用，最终减少心脏破裂发生的作用。

The changes in dietary structure caused by the rapid development of society have increased the incidence of cardiovascular disease (CVD) year by year. Acute myocardial infarction (AMI) has a rapid onset and high mortality, which greatly aggravates Chinese society. Although with the application and popularization of cardiovascular interventional technology, the short-term and long-term prognosis of patients with acute myocardial infarction (AMI), especially ST-elevation myocardial infarction (STEMI) All have been greatly improved, but the application of percutaneous coronary intervention (PCI) cannot completely prevent the occurrence of post-infarction mechanical complication after ST-segment elevation myocardial infarction. develop. Compared with heart failure and malignant arrhythmia after acute myocardial infarction, although the incidence of mechanical complications after myocardial infarction is lower, the mortality rate is extremely high, especially left ventricular free wall rupture (Post-infarction cardiac rupture) is the most dangerous. The disease progresses rapidly, and the mortality rate is close to 100%. Although it has been reported that surgical glue or a patch with collagen fibers can be used to seal myocardial ruptures through surgical techniques, more than 35% of postoperative patients still die in the hospital. Therefore, it is of great clinical value to improve the prevention of such complications after myocardial infarction. This research paper is dedicated to providing a promising drug intervention method for preventing cardiac rupture after myocardial infarction, and describing its main mechanism of action and cellular targets, so as to provide a scientific basis for possible clinical trials in the future.

Mechanical complications after myocardial infarction are divided into ventricular septal perforation, papillary muscle rupture and cardiac rupture according to the location of myocardial tear. They are the most dangerous and serious complications of acute myocardial infarction. After acute myocardial infarction, myocardial injury and repair mechanisms are rapidly activated. Myocardium in the ischemic infarction area undergoes necrosis and disintegration due to ischemia and hypoxia. Chemokines released from myocardial tissue damage enter the blood to activate and recruit inflammatory immune cells and inflammatory cells. Recognize and adhere to the damaged endothelium, then cross the myocardial microvascular endothelial barrier, enter the interstitium of cardiomyocytes to engulf necrotic and apoptotic cells, secrete cytokines to remodel the extracellular matrix, and myocardial fibroblasts, which are responsible for repairing the myocardium, also remodel the extracellular matrix. The infarcted area and the surrounding area chemotactically migrate into the infarcted area. After stimulation by cytokines, such as transforming growth factor β, the function of myocardial fibroblasts is activated and transformed into myofibroblasts, which secrete a large amount of various collagen fibers, and mucopolysaccharide rebuilds the extracellular matrix. and myocardial tissue repair. Excessive myocardial injury or insufficient myocardial repair after acute myocardial infarction can easily lead to the occurrence and progression of cardiac rupture.
Macrophages are involved in the damage and repair of various tissues and organs. In the early stage after acute myocardial infarction, a large number of macrophages infiltrate the myocardial tissue space and polarize to M1. M1 macrophages can aggravate the post-acute myocardial infarction in various ways. Damage to the heart muscle causes the heart to rupture. On the one hand, M1-type macrophages secrete a variety of inflammatory factors after functional activation, including inflammatory factors of the interleukin family and tumor necrosis factor family. , endothelial cells and myocardial fibroblasts can activate downstream pathways by binding to receptors acting on the surface of these target cells, leading to cell necrosis or apoptosis, releasing oxygen free radicals to promote lipid peroxidation in infarcted myocardial tissue cells; at the same time, cardiovascular disease It can cause increased systemic lipid peroxidation and oxidative stress levels, mainly manifested as plasma metabolites glycerophospholipid (GPL), oxidized phospholipid (oxPL), and polyunsaturated fatty acids (polyunsaturated fatty acids) acids, PUFAs) downstream metabolites, such as arachidonic acid and linoleic acid, were significantly increased, and the myocardial microenvironment and systemic lipid peroxidation could induce cells in the myocardial tissue in the infarct and surrounding areas that were conducive to myocardial repair. For example, ferroptosis of cardiac fibroblasts hinders myocardial repair and increases the risk of cardiac rupture. On the other hand, the up-regulation of inflammatory factors and ROS activation after myocardial infarction can promote the polarization of mature macrophages to pro-inflammatory macrophages, and in this process, the classical inflammatory activation pathway NF-κB and the non-canonical pathway C/EBPβ are blocked. After activation, it synergistically upregulates the transcription and expression of metalloproteinase family genes, resulting in excessive decomposition and loss of extracellular matrix, aggravating myocardial injury, and increasing the risk of mechanical complications after myocardial infarction.

This research paper is dedicated to demonstrating that a drug combination (Traditional Chinese medicine Tongxinluo, loading-dose atorvastatin and nicorandil) has a significant preventive effect on cardiac rupture after myocardial infarction, and elaborates that it is mainly mediated by inhibition of macrophage polarization The excessive decomposition of extracellular matrix and ferroptosis of myocardial fibroblasts play a role in improving myocardial injury and promoting myocardial repair, and ultimately reducing the occurrence of cardiac rupture.