Li Lihua, Weng Zhiyong, Yao Chenjuan, Song Yuanlin, Ma Tonghui
Liaoning Medical University, Department of Cell Biology, Jinzhou, PR China.
The University of Tokushima Graduate School, Department of Molecular Oral Physiology, Tokushima, Japan.
Sci Rep. 2015 Sep 8;5:13807. doi: 10.1038/srep13807.
Many studies have determined that AQP1 plays an important role in edema formation and resolution in various tissues via water transport across the cell membrane. The aim of this research was to determine both if and how AQP1 is associated with cardiac ischemic injury, particularly the development of edema following myocardial infarction (MI). AQP1+/+ and AQP1-/- mice were used to create the MI model. Under physiological conditions, AQP1-/- mice develop normally; however, in the setting of MI, they exhibit cardioprotective properties, as shown by reduced cardiac infarct size determined via NBT staining, improved cardiac function determined via left ventricular catheter measurements, decreased AQP1-dependent myocardial edema determined via water content assays, and decreased apoptosis determined via TUNEL analysis. Cardiac ischemia caused by hypoxia secondary to AQP1 deficiency stabilized the expression of HIF-1α in endothelial cells and subsequently decreased microvascular permeability, resulting in the development of edema. The AQP1-dependent myocardial edema and apoptosis contributed to the development of MI. AQP1 deficiency protected cardiac function from ischemic injury following MI. Furthermore, AQP1 deficiency reduced microvascular permeability via the stabilization of HIF-1α levels in endothelial cells and decreased cellular apoptosis following MI.
许多研究已确定水通道蛋白1(AQP1)通过跨细胞膜的水转运在各种组织的水肿形成和消退中发挥重要作用。本研究的目的是确定AQP1是否以及如何与心脏缺血性损伤相关,特别是心肌梗死(MI)后水肿的发展。使用AQP1+/+和AQP1-/-小鼠建立MI模型。在生理条件下,AQP1-/-小鼠正常发育;然而,在MI的情况下,它们表现出心脏保护特性,通过NBT染色确定的心脏梗死面积减小、通过左心室导管测量确定的心脏功能改善、通过含水量测定确定的AQP1依赖性心肌水肿减少以及通过TUNEL分析确定的细胞凋亡减少均表明了这一点。由AQP1缺乏继发的缺氧引起的心脏缺血稳定了内皮细胞中缺氧诱导因子-1α(HIF-1α)的表达,随后降低了微血管通透性,导致水肿的发展。AQP1依赖性心肌水肿和细胞凋亡促成了MI的发展。AQP1缺乏保护心脏功能免受MI后的缺血性损伤。此外,AQP1缺乏通过稳定内皮细胞中HIF-1α水平降低微血管通透性,并减少MI后的细胞凋亡。