Effects Of Gigantol On Human Retinal Microvascular Endothelial Cells Induced By High Glucose

OBJECTIVE : This study aims to investigate the effects of gigantol on aldose reductase(AR)pathway,oxidative stress,and its downstream pathway in human retinal microvascular endothelial cells(HRMECs)induced by high glucose.METHODS:HRMECs cultured in vitro were incubated with high glucose,and gigantol and epalrestat were used for intervention treatment respectively.MTS assay was performed to measure cell vitality.DCFH-DA fluorescent probe was used to detect reactive oxygen species(ROS)levels.Western blotting was performed to detect the protein expression of nuclear factor kappa B(NF-?B),the phosphorylated protein expression of phosphatidylinositol 3-kinase(p-PI3K)and protein kinase B(p-AKT).AR,hypoxia inducible factor-1?(HIF-1?),vascular endothelial growth factor(VEGF),B-cell lymphoma-2(Bcl-2)and Bcl-2 Associated X Protein(Bax)mRNA levels were measured by qRT-PCR.RESULTS: MTS results showed that cell vitality was the highest after treated with 5?mol/L gigantol or 1?mol/L epalrestat for 48 H.DCFH-DA fluorescent probe showed that gigantol reduced ROS generation obviously.Compared to the normal glucose group,protein expressions of NF-?B,p-PI3 K and p-AKT,mRNA expressions of AR,HIF-1?,VEGF,Bax/Bcl-2 were all increased in high glucose group.Compared to the high glucose group,gigantol group were all decreased.And the expression trends of AR and NF-?B in epalrestat group were consistent with gigantol group.Compared with the normal group,there was no significant difference in the expression of each factor in the mannitol group.CONCLUSION:Gigantol could inhibit high glucose induced oxidative stress and the activation of AR/NF-?B pathway and PI3K/AKT pathway in HRMECs.Gigantol may have a protective effect on diabetic retinopathy(DR).