Puerarin attenuates myocardial ischemic injury and endoplasmic reticulum stress by upregulating the Mzb1 signal pathway

作者：Jiaojiao Xue, Haolin Ren, Qí Zhāng, Jing Gu, Qian Xu, Jiaxi Sun, Lu Zhang, Ming-Sheng Zhou · 发表于：Frontiers in Pharmacology · 年份：2024 · DOI：10.3389/fphar.2024.1442831 · 被引用次数：11 · 研究领域：Kruppel-like factors research、Genetic Syndromes and Imprinting、Endoplasmic Reticulum Stress and Disease

Objective This study investigated the role of Mzb1 in puerarin protection against heart injury and dysfunction in acute myocardial infarction (AMI) mice. Methods C57BL/6 mice were pretreated with and without puerarin at doses of 50 mg/kg and 100 mg/kg for 14 days before establishing the AMI model. An AMI model was induced by ligating the left descending anterior coronary artery, and AC16 cardiomyocytes were treated with H 2 O 2 in vitro . Echocardiography was performed to measure cardiac function. DHE staining, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase assay, and DCFH-DA oxidative fluorescence staining were used to determine reactive oxygen species (ROS) production in vivo and in vitro . Bioinformatics analysis was used to predict potential upstream transcription factors of Mzb1. Results Puerarin dose-dependently reduced myocardial infarction area and injury, accompanied by the improvement of cardiac function in AMI mice. AMI mice manifested an increase in myocardial oxidative stress, endoplasmic reticulum (ER) stress, apoptosis, and mitochondrial biogenesis dysfunction, which were inhibited by pretreatment with puerarin. Puerarin also prevented Mzb1 downregulation in the hearts of AMI mice or H 2 O 2 -treated AC16 cells. Consistent with the in vivo findings, puerarin inhibited H 2 O 2 -induced cardiomyocyte apoptosis, ER stress, and mitochondrial dysfunction, which were attenuated by siRNA Mzb1. Furthermore, the JASPAR website predicted that KLF4 may be a t...