Mai Huade, Liu Chenghong, Fu Biwei, Ji Xinbo, Chen Minghui, Zhang Yunbo, Lin Yunyun, Chen Juming, Song Yanling, Gu Shenhong
Department of General Practice of The First Affiliated Hospital of Hainan Medical University Haikou 570102, Hainan, China.
Hainan Medical University Haikou 570102, Hainan, China.
Am J Transl Res. 2025 Mar 15;17(3):2293-2310. doi: 10.62347/FKNZ9461. eCollection 2025.
To explore the therapeutic effects of Carnosic acid (CA) on diabetic retinopathy (DR), a complication of diabetes mellitus (DM) characterized by retinal neuronal damage induced by oxidative stress.
DR was induced in rodent models via streptozotocin (STZ) administration, while human retinal microvascular endothelial cells (HRMECs) were cultured in high-glucose (HG) conditions. The effects of CA on oxidative stress, inflammation, and apoptotic signaling were evaluated by quantifying relevant biomarkers.
CA treatment significantly increased the expression of sirtuin 1, which was reduced in both STZ-treated rats and HG-exposed HRMECs, as confirmed by polymerase chain reaction (PCR) analysis. CA alleviated oxidative stress, inflammation, and apoptosis in STZ-induced DR models. In vitro, CA exhibited a dose-dependent enhancement of SIRT1 expression, providing substantial protection against HG-induced damage in HRMECs. This protective effect involved the suppression of oxidative mediators, reduction of pro-inflammatory cytokine release, and inhibition of apoptotic pathways. Additionally, CA prevented retinal ferroptosis by activating the SIRT1/p53/solute carrier family 7 member 11 (SLC7A11) pathway both in vivo and in vitro.
This study suggests that CA alleviates DR by activating SIRT1, leading to decreased inflammation, apoptosis, and oxidative stress.
探讨肌醇六磷酸（CA）对糖尿病视网膜病变（DR）的治疗作用，糖尿病视网膜病变是糖尿病（DM）的一种并发症，其特征是由氧化应激诱导的视网膜神经元损伤。
通过给予链脲佐菌素（STZ）在啮齿动物模型中诱导糖尿病视网膜病变，同时在高糖（HG）条件下培养人视网膜微血管内皮细胞（HRMECs）。通过量化相关生物标志物来评估CA对氧化应激、炎症和凋亡信号传导的影响。
聚合酶链反应（PCR）分析证实，CA治疗显著增加了sirtuin 1的表达，在STZ处理的大鼠和HG暴露的HRMECs中sirtuin 1的表达均降低。CA减轻了STZ诱导的糖尿病视网膜病变模型中的氧化应激、炎症和凋亡。在体外，CA呈剂量依赖性增强SIRT1表达，为HRMECs提供了对HG诱导损伤的实质性保护。这种保护作用包括抑制氧化介质、减少促炎细胞因子释放以及抑制凋亡途径。此外，CA在体内和体外均通过激活SIRT1/p53/溶质载体家族7成员11（SLC7A11）途径预防视网膜铁死亡。
本研究表明，CA通过激活SIRT1减轻糖尿病视网膜病变，导致炎症、凋亡和氧化应激减少。
