Department of Ophthalmology, 309th Hospital of PLA, Beijing, China.
Br J Pharmacol. 2013 Jun;169(3):619-31. doi: 10.1111/bph.12163.
Retinopathy, as a common complication of diabetes, is a leading cause of reduced visual acuity and acquired blindness in the adult population. The aim of present study was to investigate the therapeutic effect of hydrogen sulfide on streptozotocin (STZ)-induced diabetic retinopathy in rats.
Rats were injected with a single i.p. injection of STZ (60 mg·kg⁻¹) to induce diabetic retinopathy. Two weeks later, the rats were treated with NaHS (i.p. injection of 0.1 mL·kg⁻¹·d⁻¹ of 0.28 mol·L⁻¹ NaHS, a donor of H₂S) for 14 weeks.
Treatment with H₂S had no significant effect on blood glucose in STZ-induced diabetic rats. Treatment with exogenous H₂S enhanced H₂S levels in both plasma and retinas of STZ-induced diabetic rats. Treatment with H₂S in STZ-treated rats improved the retinal neuronal dysfunction marked by enhanced amplitudes of b-waves and oscillatory potentials and expression of synaptophysin and brain-derived neurotrophic factor, alleviated retinal vascular abnormalities marked by reduced retinal vascular permeability and acellular capillary formation, decreased vitreous VEGF content, down-regulated expressions of HIF-1α and VEGFR2, and enhanced occludin expression, and attenuated retinal thickening and suppressed expression of extracellular matrix molecules including laminin β1 and collagen IVα3 expression in retinas of STZ-induced diabetic rats. Treatment with H₂S in retinas of STZ-induced diabetic rats abated oxidative stress, alleviated mitochondrial dysfunction, suppressed NF-κB activation and attenuated inflammation.
Treatment with H₂S alleviates STZ-induced diabetic retinopathy in rats possibly through abating oxidative stress and suppressing inflammation.
糖尿病性视网膜病变是一种常见的并发症,也是成年人视力下降和获得性失明的主要原因。本研究旨在探讨硫化氢对链脲佐菌素(STZ)诱导的糖尿病大鼠视网膜病变的治疗作用。
大鼠一次性腹腔注射 STZ(60mg·kg⁻¹)诱导糖尿病视网膜病变。2 周后,大鼠用 NaHS(腹腔注射 0.28mol·L⁻¹NaHS,H₂S 的供体,0.1mL·kg⁻¹·d⁻¹)治疗 14 周。
H₂S 处理对 STZ 诱导的糖尿病大鼠血糖无明显影响。外源性 H₂S 处理可提高 STZ 诱导的糖尿病大鼠血浆和视网膜中 H₂S 水平。在 STZ 处理的大鼠中,H₂S 处理可改善视网膜神经元功能障碍,表现为 b 波和振荡电位幅度增强以及突触小体蛋白和脑源性神经营养因子表达增强,减轻视网膜血管异常,表现为视网膜血管通透性降低和无细胞毛细血管形成减少,玻璃体内 VEGF 含量降低,HIF-1α 和 VEGFR2 表达下调,occludin 表达增强,并减轻视网膜增厚,抑制细胞外基质分子包括层粘连蛋白 β1 和Ⅳ型胶原α3 在视网膜中的表达。在 STZ 诱导的糖尿病大鼠视网膜中,H₂S 处理可减轻氧化应激,缓解线粒体功能障碍,抑制 NF-κB 激活,减轻炎症。
H₂S 处理可减轻 STZ 诱导的糖尿病大鼠的糖尿病视网膜病变,可能通过减轻氧化应激和抑制炎症。