Gliquidone improves retinal injury to relieve diabetic retinopathy via regulation of SIRT1/Notch1 pathway

BMC Ophthalmology

Zhenhua Zhang¹  Shasha Sun¹  Lijun Zhang¹  Mengdan Yu¹ 

[1] Department of Ophthalmology, Affiliated Qingdao Central Hospital, Qingdao University, No. 127, Siliu South Road, 266042, Qingdao City, Shandong Province, China;

关键词: Gliquidone;    diabetic retinopathy;    inflammation;    oxidative stress;    SIRT1/Notch1 pathway;   

DOI  :  10.1186/s12886-021-02215-8

来源: Springer

【 摘 要 】

BackgroundDiabetic retinopathy (DR) is a common and potentially devastating microvascular complication of diabetes mellitus (DM). The main features of DR are inflammation and oxidative damage. Gliquidone (GLI) is confirmed to be a hypoglycemic drug by oral administration. The current study is aimed to investigate the role and mechanism of GLI on the pathogenesis of DR.MethodsHigh glucose (HG)-induced human retinal endothelial cells (HRECs) were used to explore the anti-inflammatory and anti-oxidant effects of GLI on DR in vitro. Streptozotocin (STZ)-induced DM rats were used to investigate the effects of GLI on retinal structures, inflammation, and oxidative stress. The levels of SIRT1/Notch1 pathway-related proteins were determined by western blotting.ResultsGLI treatment promoted the viability and inhibited the apoptosis of HG-induced HRECs. Meanwhile, the levels of interleukin (IL)-6, IL-1β, tumour necrosis factor alpha and reactive oxygen species were suppressed, while both catalase and superoxide dismutase were elevated after GLI treatment in HG-induced HRECs. Furthermore, we found that Silencing information regulator 2 related enzyme 1 (SIRT1) silencing reversed the inhibiting effects of GLI on the levels of protein Notch1 and effector genes Hes1 and Hey2. Similar anti-inflammatory and anti-oxidant effects of GLI in STZ-induced DM rats were observed. Additionally, GLI administration also repressed vascular hyperpermeability in vivo.ConclusionGLI may be an effective agent to improve DR through repression of inflammation and oxidative stress via SIRT1/Notch1 pathway.

【 授权许可】

CC BY