背景:急性心肌梗死(AMI)是全球死亡的主要原因,由于富含胶原蛋白的瘢痕组织取代坏死的心肌细胞,弹性蛋白/胶原蛋白比率降低加剧了心脏功能障碍。本研究旨在评估吡非尼酮对AMI后早期心功能的治疗作用,并阐明其对弹性蛋白/胶原比值的影响。
方法:Sprague-Dawley大鼠分为4组:假,AMI,用PBS(AMI-PBS)处理的AMI,和用吡非尼酮治疗的AMI(AMI-PFD)(各n=12)。通过冠状动脉结扎诱导AMI。AMI-PFD和AMI-PBS组接受吡非尼酮和PBS治疗14天,分别。心功能,纤维化,血清细胞因子,胶原蛋白和弹性蛋白含量,并对其比率进行了评估。来自新生大鼠的心脏成纤维细胞(CFs)被归类为对照,缺氧诱导(LO),LO+PBS,和LO+PFD组。ELISA检测炎症因子,和RT-PCR分析胶原蛋白和弹性蛋白基因的表达。
结果:AMI-PFD组心功能改善,血清白细胞介素-1β(IL-1β)降低,IL-6和转化生长因子-β(TGF-β)。I型和III型胶原降低22.6%(P=0.0441)和34.4%(P=0.0427),分别,弹性蛋白含量增加了79.4%(P=0.0126)。E/COLI和E/COLIII比率分别上升了81.1%(P=0.0026)和88.1%(P=0.0006)。LO+PFD组的CFs表现出IL-1β降低,IL-6,TGF-β,I型和III型胶原蛋白,随着弹性蛋白mRNA的增加,增强弹性蛋白/胶原蛋白比例。
结论:吡非尼酮通过增加AMI后的早期弹性蛋白/胶原比率来增强心脏功能。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: Pirfenidone enhances cardiac function by augmenting the early elastin/collagen ratio post-AMI.