关键词: 牡荆苷, AMPK/SIRT1, 糖尿病视网膜病变, 血管生成, 氧化损伤

Abstract:

This study explores the impacts of vitexin (Vit) on angiogenesis and oxidative damage in rats with diabetic retinopathy (DR)  by adjusting adenosine monophosphate activated protein kinase/silent information regulator 1 (AMPK/SIRT1) signaling pathway. DR rats were constructed and randomly assigned into a normal group, a model group, a low-dose Vit group, a high-dose Vit group, a calcium dobesilate positive control group, and a high-dose Vit+AMPK inhibitor BML-275 group, each had 12 rats. The changes in body mass and fasting blood glucose (FBG) of rats were examined. ELISA method was used to detect oxidative stress and inflammatory markers. Fluorescein fundus angiography was performed to detect retinal angiogenesis. PAS staining was performed to observe changes in retinal microvasculature. HE staining was used to observe pathological changes in retinal tissue. Molecular docking analysis of Vit's binding ability to proteins involved in angiogenesis and the AMPK/SIRT1 pathway. Western blot was used to measure angiogenesis and AMPK/SIRT1 pathway proteins. Results show that compared with the model group, the low-dose Vit group, high-dose Vit group, and positive control group showed reduced retinal tissue structure damage, decreased neovascularization, more uniform vascular diameter, reduced the average optical density value of fluorescein leakage, microvascular generation, FBG, serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), lipid peroxidation (LPO), total antioxidant capacity (T-AOC) levels, and retinal tissue hypoxia inducible factor-1 subunit α (HIF-1α), vascular endothelial growth factor (VEGF), and intercellular adhesion molecule-1 (ICAM-1) proteins (P<0.01), and increased body weight, retinal tissue p-AMPK/AMPK and SIRT1 proteins (P<0.05). BML-275 reversed the inhibitory effects of high-dose Vit group on angiogenesis, oxidative damage, and inflammatory response in DR rats, further exacerbating pathological damage to retinal tissue (P<0.01). The binding capacity of Vit to AMPK, SIRT1, HIF-1α, VEGF, ICAM-1 are all relatively good. In conclusion, Vit may improve angiogenesis and oxidative damage in DR rats by activating the AMPK/SIRT1 signaling pathway.

Key words:

vitexin; AMPK/SIRT1, diabetic retinopathy, angiogenesis, oxidative damage