Effect of sesamin on high glucose-induced vascular endothelial cell injury through lncRNA WEE2-AS1/miR-515-5p pathway

ObjectiveTo explore the effect of sesamin on human umbilical vein endothelial cells (HUVEC) injury induced by high glucose and its possible mechanism.

MethodsHigh glucose stimulated the HUVEC to establish the cell damage model, and the cells were treated with different concentrations of sesamin.qRT-PCR was used to detect the expressions of LncRNA WEE2-AS1 and miR-515-5p.After transfection of sh-NC and sh-WEE2-AS1 into HUVEC, the cells were treated with 30 mmol/L glucose(HG+sh-NC group, HG+sh-WEE2-AS1 group).HUVEC cells stably overexpressing WEE2-AS1 were constructed.HG+WEE2-AS1-LV group was treated with 30 mmol/L glucose.HG+SES+WEE2 -AS1-LV group was treated with 40 μmol/L sesamin and 30 mmol/L glucose.MTT and flow cytometry were used to detect cell proliferation and apoptosis rates.The levels of SOD, LDH, and MDA were tested according to the kit instructions.The dual luciferase reporter gene experiment was used to detect the targeting relationship between WEE2-AS1 and miR-515-5p.Western blotting was used to detect the expression of cleaved-caspase3 protein.

ResultsSesamin reduced the expression of WEE2-AS1, the rate of apoptosis, the protein level of cleaved-caspase3, the activity of LDH and the level of MDA in HUVEC after stimulated with high glucose (P < 0.05).It could promote the expression of miR-515-5p and enhance the cell viability and the activity of SOD (P < 0.05) in a dose-dependent manner.Compared with the HG+sh-NC group, the expression of miR-515-5p in the HG+sh-WEE2-AS1 group was increased (P < 0.05), the cell viability and the activity of SOD were increased (P < 0.05), and apoptosis rate and the protein level of cleaved-caspase3 were decreased (P < 0.05), and the activity of LDH and the level of MDA were decreased (P < 0.05).WEE2-AS1 could targetedly regulate miR-515-5p.Compared with the HG+SES group, the expression of miR-515-5p in the HG+SES+WEE2-AS1-LV group was decreased (P < 0.05), the cell viability and the activity of SOD were decreased (P < 0.05), the apoptosis rate and the protein level of cleaved-caspase3 were increased (P < 0.05), the activity of LDH and the level of MDA were increased (P < 0.05).

ConclusionsSesamin can promote cell proliferation and inhibit apoptosis and oxidative stress by regulating WEE2-AS1/miR-515-5p, thereby reducing the damage of vascular endothelial induced by high glucose.