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Abstract：
Diabetic retinopathy (DR) severely affects vision in individuals with diabetes. High glucose (HG) induces oxidative stress in retinal cells, a key contributor to DR development. Previous studies suggest that fibroblast growth factor-1 (FGF-1) can mitigate hyperglycemia and protect tissues from HG-induced damage. However, the specific effects and mechanisms of FGF-1 on DR remain unclear. In our study, FGF-1-pretreated adult retinal pigment epithelial (ARPE)-19 cells were employed to investigate. Results indicate that FGF-1 significantly attenuated HG-induced oxidative stress, including reactive oxygen species, DNA damage, protein carbonyl content, and lipid peroxidation. FGF-1 also modulated the expression of oxidative and antioxidative enzymes. Mechanistic investigations showed that HG induced high endoplasmic reticulum (ER) stress and upregulated specific proteins associated with apoptosis. FGF-1 effectively alleviated ER stress, reduced apoptosis, and restored autophagy through the adenosine monophosphate-activated protein kinase/mammalian target of the rapamycin signaling pathway. We observed that the changes induced by HG were dose-dependently reversed by FGF-1. Higher concentrations of FGF-1 (5 and 10 ng/mL) exhibited increased effectiveness in mitigating HG-induced damage, reaching statistical significance (p < 0.05). In conclusion, our study underscores the promising potential of FGF-1 as a safeguard against DR. FGF-1 emerges as a formidable intervention, attenuating oxidative stress, ER stress, and apoptosis, while concurrently promoting autophagy. This multifaceted impact positions FGF-1 as a compelling candidate for alleviating retinal cell damage in the complex pathogenesis of DR.
摘要：
糖尿病视网膜病变（DR）严重影响糖尿病患者的视力。高糖（HG）诱导视网膜细胞氧化应激，DR开发的关键贡献者。先前的研究表明，成纤维细胞生长因子-1（FGF-1）可以减轻高血糖症并保护组织免受HG诱导的损伤。然而,FGF-1对DR的具体作用和机制尚不清楚.在我们的研究中,采用FGF-1预处理的成人视网膜色素上皮（ARPE）-19细胞进行研究。结果表明FGF-1显著减弱HG诱导的氧化应激，包括活性氧，DNA损伤,蛋白质羰基含量，和脂质过氧化。FGF-1还调节氧化和抗氧化酶的表达。机制研究表明，HG可诱导高内质网（ER）应激并上调与凋亡相关的特定蛋白。FGF-1有效缓解内质网应激,减少细胞凋亡，并通过雷帕霉素信号通路的一磷酸腺苷激活的蛋白激酶/哺乳动物靶蛋白恢复自噬。我们观察到HG诱导的变化被FGF-1剂量依赖性地逆转。更高浓度的FGF-1（5和10ng/mL）在减轻HG诱导的损伤方面表现出更高的有效性，达到统计学意义(p<0.05)。总之,我们的研究强调了FGF-1作为预防DR的潜在潜力.FGF-1作为一种强大的干预措施出现，减弱氧化应激，ER压力,和细胞凋亡，同时促进自噬。这种多方面的影响使FGF-1成为减轻DR复杂发病机制中视网膜细胞损伤的令人信服的候选者。
