Role of necroptosis and p38 MAPK inhibition in the protective effects of H2S against HG-induced cytotoxicity in HUVECs. (A) HUVECs were treated with 40 mM HG for 24 h with or without the pretreatment with 400 µM NaHS for 30 min or 3 µM SB203580 (the inhibitor of p38) for 60 min and the cell viability was analyzed using a CCK-8 assay. HUVECs were treated with 40 mM HG for 24 h with or without pretreatment with (B) 100 µM Nec-1 or transfection with (C) RIP3-siRNA for 24 h and the cell viability was analyzed using a CCK-8 assay. Data are presented as the mean ± SEM (n=5). **P<0.01 vs. control group; #P<0.05, ##P<0.01 vs. HG group. NaHS, sodium hydrosulfide; HG, high glucose; HUVECs, human umbilical vein endothelial cells; RIP3, receptor-interacting protein 3; siRNA, small interfering RNA; Nec-1, necrostatin-1.