Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Spain.
Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Spain.
J Diabetes Complications. 2017 Oct;31(10):1481-1490. doi: 10.1016/j.jdiacomp.2017.07.009. Epub 2017 Jul 26.
Calcium dobesilate (CaD) is beneficial in early stages of diabetic retinopathy (DR), but its mechanisms of action remains to be elucidated. The aim was to investigate the effect of CaD on proinflammatory cytokines and oxidative stress.
db/db mice were randomly assigned to daily oral treatment with CaD (200mg/kg/day) or vehicle for 15days. Biomarkers of oxidative stress (dihydroethidium, malondialdehyde), NF-κB, and proinflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α, MCP-1) were examined in the retina by immunohistochemical analysis. Cultures of human retinal endothelial cells (HRECs) were used for complementary experiments.
CaD significantly reduced the biomarkers of oxidative stress in the retina of db/db mice. In addition, CaD prevented the increase of NF-κB, IL-6, IL-8, TNF-α and MCP-1 induced by diabetes. CaD inhibited the activation of NF-kβ induced by IL-1β by preventing IKKB-α phosphorylation in HRECs and reduced the upregulation of IL-6 and IL-18 induced by TNF-α in a dose-dependent manner.
Our results suggest that antioxidant and antiinflammatory effects are crucial in accounting for the effectiveness of CaD for treating DR.
羟苯磺酸钙（CaD）在糖尿病视网膜病变（DR）的早期阶段有益，但作用机制仍需阐明。本研究旨在探讨 CaD 对促炎细胞因子和氧化应激的影响。
将 db/db 小鼠随机分为每日口服 CaD（200mg/kg/天）或载体治疗 15 天。通过免疫组织化学分析检测视网膜中氧化应激生物标志物（二氢乙啶、丙二醛）、NF-κB 和促炎细胞因子（IL-1β、IL-6、IL-8、TNF-α、MCP-1）。使用人视网膜内皮细胞（HRECs）进行补充实验。
CaD 可显著降低 db/db 小鼠视网膜中氧化应激的生物标志物。此外，CaD 可预防糖尿病诱导的 NF-κB、IL-6、IL-8、TNF-α和 MCP-1的增加。CaD 通过阻止 HRECs 中 IKKB-α 的磷酸化来抑制由 IL-1β诱导的 NF-kβ 的激活，并以剂量依赖性方式降低 TNF-α诱导的 IL-6 和 IL-18 的上调。
我们的研究结果表明，抗氧化和抗炎作用对于解释 CaD 治疗 DR 的有效性至关重要。
