Department of Geratology, Jiangnan University Medical Center, JUMC, Wuxi, Jiangsu Province, China.
Physiol Res. 2023 Apr 30;72(2):177-186. doi: 10.33549/physiolres.934992.
Oxidative stress closely related to the progression and severity of myocardial infarction (MI). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) is one of the major enzymes that generate reactive oxygen species (ROS) in cardiovascular system. Here, we aim to elucidate the pathological role of NOX4 in MI. MI mouse model was created by the coronary artery ligation. NOX4 was specifically knocked down in heart through intramyocardial injection of siRNA. NOX4 expression and oxidative stress indicators were determined at different time points using qRT-PCR, Western blot, and ELISA, and then analyzed by Pearson's correlation. Cardiac function was evaluated by using echocardiographic technique. NOX4 was upregulated in myocardial tissues of MI mice, which positively correlated with the elevation of oxidative stress indicators. Knockdown of NOX4 in heart significantly reduced the production of ROS and the level of oxidative stress in left ventricle tissues, which was accompanied by significant improvement of cardiac function in MI mice. Selective knockdown of NOX4 in heart attenuates MI-induced oxidative stress and improves cardiac function, suggesting inhibition of NOX4/ROS axis in heart using siRNA is a potential therapeutic treatment for MI-induced cardiac dysfunction.
氧化应激与心肌梗死（MI）的进展和严重程度密切相关。烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶 4（NOX4）是心血管系统中产生活性氧（ROS）的主要酶之一。在这里，我们旨在阐明 NOX4 在 MI 中的病理作用。通过冠状动脉结扎创建 MI 小鼠模型。通过心肌内注射 siRNA 特异性敲低心脏中的 NOX4。使用 qRT-PCR、Western blot 和 ELISA 在不同时间点测定 NOX4 表达和氧化应激指标，并通过 Pearson 相关性进行分析。使用超声心动图技术评估心脏功能。MI 小鼠心肌组织中 NOX4 上调，与氧化应激指标的升高呈正相关。心脏中 NOX4 的敲低显著减少了 ROS 的产生和左心室组织中的氧化应激水平，这伴随着 MI 小鼠心脏功能的显著改善。心脏中选择性敲低 NOX4 可减轻 MI 诱导的氧化应激并改善心脏功能，表明使用 siRNA 抑制心脏中的 NOX4/ROS 轴可能是治疗 MI 诱导的心脏功能障碍的一种潜在治疗方法。
