Wogonoside alleviates high glucose-induced dysfunction of retinal microvascular endothelial cells and diabetic retinopathy in rats by up-regulating SIRT1.
10.12122/j.issn.1673-4254.2022.04.02
- Author:
Xiao Li SHAO
1
;
Jiang Yi YU
1
;
Wei Hui NI
2
Author Information
1. First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China.
2. Department of Endocrinology, BenQ Medical Center Affiliated to Nanjing Medical University, Nanjing 210029, China.
- Publication Type:Journal Article
- Keywords:
abnormal proliferation;
diabetic retinopathy;
inflammation;
oxidative stress;
wogonoside
- MeSH:
Animals;
Diabetes Mellitus/metabolism*;
Diabetic Retinopathy/metabolism*;
Endothelial Cells;
Flavanones;
Glucose/pharmacology*;
Glucosides;
Inflammation/metabolism*;
Interleukin-6/metabolism*;
Neovascularization, Pathologic/metabolism*;
Rats;
Reactive Oxygen Species/metabolism*;
Sirtuin 1/metabolism*;
Streptozocin/pharmacology*;
Vascular Endothelial Growth Factor A/metabolism*
- From:
Journal of Southern Medical University
2022;42(4):463-472
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effects of wogonoside on high glucose-induced dysfunction of human retinal microvascular endothelial cells (hRMECs) and streptozotocin (STZ)-induced diabetic retinopathy in rats and explore the underlying molecular mechanism.
METHODS:HRMECs in routine culture were treated with 25 mmol/L mannitol or exposed to high glucose (30 mmol/L glucose) and treatment with 10, 20, 30, 40 μmol/L wogonoside. CCK-8 assay and Transwell assay were used to examine cell proliferation and migration, and the changes in tube formation and monolayer cell membrane permeability were tested. ROS, NO and GSH-ST kits were used to evaluate oxidative stress levels in the cells. The expressions of IL-1β and IL-6 in the cells were examined with qRT-PCR and ELISA, and the protein expressions of VEGF, HIF-1α and SIRT1 were detected using Western blotting. We also tested the effect of wogonoside on retinal injury and expressions of HIF-1α, ROS, VEGF, TNF-α, IL-1β, IL-6 and SIRT1 proteins in rat models of STZ-induced diabetic retinopathy.
RESULTS:High glucose exposure caused abnormal proliferation and migration, promoted angiogenesis, increased membrane permeability (P < 0.05), and induced inflammation and oxidative stress in hRMECs (P < 0.05). Wogonoside treatment concentration-dependently inhibited high glucose-induced changes in hRMECs. High glucose exposure significantly lowered the expression of SIRT1 in hRMECs, which was partially reversed by wogonoside (30 μmol/L) treatment; interference of SIRT1 obviously attenuated the inhibitory effects of wogonoside against high glucose-induced changes in proliferation, migration, angiogenesis, membrane permeability, inflammation and oxidative stress in hRMECs. In rat models of STZ-induced diabetic retinopathy, wogonoside effectively suppressed retinal thickening (P < 0.05), alleviated STZ-induced retinal injury, and increased the expression of SIRT1 in the retinal tissues (P < 0.001).
CONCLUSION:Wogonoside alleviates retinal damage caused by diabetic retinopathy by up-regulating SIRT1 expression.
