Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China.
Mol Med Rep. 2021 Jan;23(1). doi: 10.3892/mmr.2020.11716. Epub 2020 Nov 25.
(IO) is an edible fungus that exerts various biological functions, including anti‑inflammatory, antitumor and immunomodulatory effects. The present study was designed to investigate the role of IO extract (IOE) in myocardial ischemia/reperfusion (MI/R) and determine the exact molecular mechanisms. The left anterior descending coronary artery was ligated to establish the MI/R injury model in rats. IOE exhibited a novel cardioprotective effect, as shown by improvement in cardiac function and decrease in infarct size. Pretreatment with IOE activated antioxidant enzymes in cardiomyocytes, including glutathione peroxidase, superoxide dismutase and catalase. IOE pretreatment also induced the upregulation of NAD‑dependent protein deacetylase sirtuin‑1 (SIRT1) and downregulation of glucose‑regulated protein 78, phosphorylated (p‑) protein kinase R‑like endoplasmic reticulum kinase, p‑eukaryotic translation initiation factor 2 subunit α, C/EBP homologous protein and ‑12. Furthermore, IOE alleviated endoplasmic reticulum (ER) stress‑induced apoptosis in cardiomyocytes by decreasing the mRNA levels of caspase‑12. IOE inhibited apoptosis induced by overexpression of pro‑caspase‑9 and pro‑caspase‑3. In summary, IOE pretreatment protects the heart against MI/R injury through attenuating oxidative damage and suppressing ER stress‑induced apoptosis, which may be primarily due to SIRT1 activation.
(IO)是一种食用真菌,具有多种生物功能,包括抗炎、抗肿瘤和免疫调节作用。本研究旨在探讨 IO 提取物(IOE)在心肌缺血/再灌注(MI/R)中的作用,并确定确切的分子机制。结扎大鼠左前降支冠状动脉建立 MI/R 损伤模型。IOE 表现出一种新的心脏保护作用,表现为改善心功能和减少梗死面积。IOE 预处理可激活心肌细胞中的抗氧化酶,包括谷胱甘肽过氧化物酶、超氧化物歧化酶和过氧化氢酶。IOE 预处理还诱导 NAD 依赖性蛋白去乙酰化酶 SIRT1 的上调和葡萄糖调节蛋白 78、磷酸化蛋白激酶 R 样内质网激酶、磷酸化真核翻译起始因子 2 亚单位 α、C/EBP 同源蛋白和 -12 的下调。此外,IOE 通过降低半胱天冬酶-12 的 mRNA 水平减轻 ER 应激诱导的心肌细胞凋亡。IOE 抑制过表达的前半胱天冬酶-9 和前半胱天冬酶-3 诱导的细胞凋亡。总之,IOE 预处理通过减轻氧化损伤和抑制 ER 应激诱导的细胞凋亡来保护心脏免受 MI/R 损伤,这可能主要归因于 SIRT1 的激活。