Henan Key Laboratory of Cardiac Remodeling and Transplantation, Zhengzhou Seventh People's Hospital, Zhengzhou, Henan 450016, China; Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, Henan 453003, China.
Henan Key Laboratory of Cardiac Remodeling and Transplantation, Zhengzhou Seventh People's Hospital, Zhengzhou, Henan 450016, China; USM-ALPS Cardiac Research Laboratory, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang 13200, Malaysia.
Biomed Pharmacother. 2024 Sep;178:117254. doi: 10.1016/j.biopha.2024.117254. Epub 2024 Aug 13.
Acute myocardial infarction (AMI) is a leading cause of mortality worldwide, with reduced elastin/collagen ratios exacerbating cardiac dysfunction due to collagen-rich scar tissue replacing necrotic myocardial cells. This study aims to evaluate pirfenidone's therapeutic effect on early cardiac function post-AMI and elucidate its impact on the elastin/collagen ratio.
Sprague-Dawley rats were divided into four groups: Sham, AMI, AMI treated with PBS (AMI-PBS), and AMI treated with pirfenidone (AMI-PFD) (n=12 each). AMI was induced via coronary artery ligation. The AMI-PFD and AMI-PBS groups received pirfenidone and PBS for 14 days, respectively. Cardiac function, fibrosis, serum cytokines, collagen and elastin content, and their ratios were assessed. Cardiac fibroblasts (CFs) from neonatal rats were categorized into control, hypoxia-induced (LO), LO+PBS, and LO+PFD groups. ELISA measured inflammatory factors, and RT-PCR analyzed collagen and elastin gene expression.
The AMI-PFD group showed improved cardiac function and reduced serum interleukin-1β (IL-1β), IL-6, and transforming growth factor-β (TGF-β). Type I and III collagen decreased by 22.6 % (P=0.0441) and 34.4 % (P=0.0427), respectively, while elastin content increased by 79.4 % (P=0.0126). E/COLI and E/COLIII ratios rose by 81.1 % (P=0.0026) and 88.1 % (P=0.0006). CFs in the LO+PFD group exhibited decreased IL-1β, IL-6, TGF-β, type I and III collagen, with increased elastin mRNA, enhancing the elastin/collagen ratio.
Pirfenidone enhances cardiac function by augmenting the early elastin/collagen ratio post-AMI.
急性心肌梗死（AMI）是全球范围内导致死亡的主要原因，由于富含胶原的疤痕组织取代坏死的心肌细胞，弹性蛋白/胶原比值降低会加剧心脏功能障碍。本研究旨在评估吡非尼酮对 AMI 后早期心功能的治疗效果，并阐明其对弹性蛋白/胶原比值的影响。
将 Sprague-Dawley 大鼠分为四组：假手术组（Sham）、AMI 组、AMI 给予磷酸盐缓冲液（AMI-PBS）组（AMI-PBS）和 AMI 给予吡非尼酮（AMI-PFD）组（AMI-PFD）（每组 12 只）。通过冠状动脉结扎诱导 AMI。AMI-PFD 和 AMI-PBS 组分别给予吡非尼酮和 PBS 治疗 14 天。评估心功能、纤维化、血清细胞因子、胶原和弹性蛋白含量及其比值。将新生大鼠的心脏成纤维细胞（CFs）分为对照组、缺氧诱导组（LO）、LO+PBS 组和 LO+PFD 组。ELISA 法检测炎症因子，RT-PCR 分析胶原和弹性蛋白基因表达。
AMI-PFD 组心功能改善，血清白细胞介素-1β（IL-1β）、IL-6 和转化生长因子-β（TGF-β）降低。I 型和 III 型胶原分别降低 22.6%（P=0.0441）和 34.4%（P=0.0427），而弹性蛋白含量增加 79.4%（P=0.0126）。E/COLI 和 E/COLIII 比值分别升高 81.1%（P=0.0026）和 88.1%（P=0.0006）。LO+PFD 组 CFs 中 IL-1β、IL-6、TGF-β、I 型和 III 型胶原降低，弹性蛋白 mRNA 增加，增加了弹性蛋白/胶原比值。
吡非尼酮通过增加 AMI 后早期的弹性蛋白/胶原比值来增强心功能。
