Vocational School of Health Services, Atatürk University, Erzurum, Turkiye; Pharmaceutical Research and Development, Graduate School of Natural and Applied Sciences, Atatürk University, Erzurum, Turkiye.
Faculty of Veterinary Medicine, Department of Pathology, Sivas Cumhuriyet University, Sivas, Turkiye.
Int Immunopharmacol. 2024 Oct 25;140:112871. doi: 10.1016/j.intimp.2024.112871. Epub 2024 Aug 6.
Diabetic keratopathy, characterized by corneal structural changes, is a common complication of diabetes mellitus (DM). Docosahexaenoic acid (DHA), an omega-3 fatty acid, has shown potential therapeutic benefits in various diabetic complications. This study aimed to investigate the protective effect of DHA on corneal tissue in streptozotocin (STZ)-induced type 2 DM in rats. Forty male Sprague-Dawley rats were randomly assigned to four groups (n = 10 per group): Control, DHA, DM, and DM + DHA. The DHA group received DHA by oral gavage at a dose of 100 mg/kg daily for 10 days. In the DM group, diabetes was induced by a single intraperitoneal injection of STZ at 50 mg/kg. Confirmation of diabetes induction was based on monitoring fasting blood glucose levels on the third day post-injection. The DM + DHA group underwent the same diabetes induction protocol with STZ and received DHA at 100 mg/kg daily via oral gavage for 10 consecutive days. Corneal tissue samples were collected at the end of the study period for histopathological, immunohistochemical, qRT-PCR, and ELISA analyses. Histopathological analysis showed significant edema, angiogenesis, and degeneration in the DM group compared to the control (p < 0.001). DHA treatment significantly mitigated these changes, approaching control levels (p < 0.01). Immunohistochemistry showed increased VEGFR2 and iNOS expression in the DM group, which was significantly reduced in the DM + DHA group (p < 0.01). qRT-PCR results indicated a significant decrease in Bcl-2 expression (p < 0.001) and an increase in ATF-6, IRE1, NF-κB, TNF-α, IL-1β, NLRP3, Bax, and Caspase-3 expressions in the DM group (p < 0.001). ELISA analyses revealed significantly elevated levels of inflammatory markers NF-κB, TNF-α, IL-1β, and IL-6 in the DM group compared to the control (p < 0.001). DHA treatment significantly upregulated Bcl-2 and downregulated apoptotic and inflammatory markers (p < 0.01). DHA demonstrated significant protective effects against STZ-induced corneal damage in diabetic rats by modulating apoptotic and inflammatory pathways. These findings suggest that DHA may be a promising therapeutic agent for preventing diabetic keratopathy.
糖尿病性角膜病变是糖尿病（DM）的一种常见并发症，其特征为角膜结构改变。二十二碳六烯酸（DHA）作为一种 ω-3 脂肪酸，在多种糖尿病并发症中显示出潜在的治疗益处。本研究旨在探讨 DHA 对链脲佐菌素（STZ）诱导的 2 型糖尿病大鼠角膜组织的保护作用。40 只雄性 Sprague-Dawley 大鼠随机分为四组（每组 10 只）：对照组、DHA 组、DM 组和 DM+DHA 组。DHA 组通过口服灌胃给予 100mg/kg DHA，每天 1 次，共 10 天。DM 组通过单次腹腔注射 50mg/kg STZ 诱导糖尿病。第 3 天通过监测空腹血糖水平来确认糖尿病的诱导。DM+DHA 组用 STZ 进行相同的糖尿病诱导方案，并通过口服灌胃给予 100mg/kg DHA，连续 10 天。研究结束时收集角膜组织样本进行组织病理学、免疫组织化学、qRT-PCR 和 ELISA 分析。组织病理学分析显示，与对照组相比，DM 组的角膜组织出现明显的水肿、血管生成和变性（p<0.001）。DHA 治疗可显著减轻这些变化，接近对照组水平（p<0.01）。免疫组织化学显示，DM 组 VEGFR2 和 iNOS 表达增加，而 DM+DHA 组表达明显减少（p<0.01）。qRT-PCR 结果表明，DM 组 Bcl-2 表达显著降低（p<0.001），ATF-6、IRE1、NF-κB、TNF-α、IL-1β、NLRP3、Bax 和 Caspase-3 表达增加（p<0.001）。ELISA 分析显示，与对照组相比，DM 组的炎症标志物 NF-κB、TNF-α、IL-1β 和 IL-6 水平显著升高（p<0.001）。DHA 治疗可显著上调 Bcl-2，下调凋亡和炎症标志物（p<0.01）。DHA 通过调节凋亡和炎症途径对 STZ 诱导的糖尿病大鼠角膜损伤具有显著的保护作用。这些发现表明，DHA 可能是预防糖尿病性角膜病变的一种有前途的治疗药物。
