达格列净是一种钠-葡萄糖协同转运蛋白 2 (SGLT2) 抑制剂，其生物效应揭示了其抗氧化和抗炎特性，表明其治疗益处超出了血糖控制范围。本研究探讨了达格列净对丙酸（PPA）诱导的自闭症谱系障碍（ASD）大鼠模型的神经保护作用，该模型的特点是社交互动缺陷、沟通障碍、重复行为、认知障碍和氧化应激。我们的研究旨在寻找自闭症谱系障碍的有效治疗方法，这种疾病的治疗选择有限，但对个人和家庭影响重大。 PPA 在啮齿类动物中诱发类似 ASD 的症状，模仿人类 ASD 的生化和行为特征。这项研究探讨了达格列净缓解这些症状的潜力，为新的治疗途径提供了见解。研究结果表明，达格列净可增强核因子红细胞 2 相关因子 2 (Nrf2) 抗氧化途径的激活，并增加神经营养因子和生长因子的水平，例如脑源性神经营养因子 (BDNF)、胰岛素样生长因子-1。 IGF-1) 和胰岛素样生长因子结合蛋白 3 (IGFBP-3)。此外，达格列净还可减少促炎细胞因子，包括肿瘤坏死因子-α (TNF-α) 和白细胞介素 17 (IL-17)，并减少氧化应激标志物丙二醛 (MDA)。达格列净的抗氧化特性通过调节细胞凋亡机制和增强抗氧化能力来支持认知功能。这些综合作用有助于减少 PPA 诱导的自闭症谱系障碍 (ASD) 中的学习和记忆障碍，凸显了达格列净作为自闭症谱系障碍 (ASD) 氧化应激和炎症相关认知衰退的辅助治疗的潜力。这项研究强调了探索针对 ASD 病理生理学分子途径的新治疗策略的重要性，这可能会改善受该疾病影响的个体的生活质量。版权所有 © 2024。由 Elsevier Inc. 出版。

The biological effects of dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, reveal its antioxidant and anti-inflammatory properties, suggesting therapeutic benefits beyond glycemic control. This study explores the neuroprotective effects of dapagliflozin in a rat model of autism spectrum disorder (ASD) induced by propionic acid (PPA), characterized by social interaction deficits, communication challenges, repetitive behaviors, cognitive impairments, and oxidative stress. Our research aims to find effective treatments for ASD, a condition with limited therapeutic options and significant impacts on individuals and families. PPA induces ASD-like symptoms in rodents, mimicking biochemical and behavioral features of human ASD. This study explores dapagliflozin's potential to mitigate these symptoms, providing insights into novel therapeutic avenues. The findings demonstrate that dapagliflozin enhances the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway and increases levels of neurotrophic and growth factors such as brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-binding protein-3 (IGFBP-3). Additionally, dapagliflozin reduces pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17), and decreases the oxidative stress marker malondialdehyde (MDA). Dapagliflozin's antioxidant properties support cognitive functions by modulating apoptotic mechanisms and enhancing antioxidant capacity. These combined effects contribute to reducing learning and memory impairments in PPA-induced ASD, highlighting dapagliflozin's potential as an adjunctive therapy for oxidative stress and inflammation-related cognitive decline in ASD. This study underscores the importance of exploring new therapeutic strategies targeting molecular pathways involved in the pathophysiology of ASD, potentially improving the quality of life for individuals affected by this disorder.Copyright © 2024. Published by Elsevier Inc.