Objective To investigate the role of 24-dehydrocholesterol reductase(DHCR24)in doxorubicin-induced senescence-related dysfunction of vascular endothelial cells.Methods Human umbilical vein endothelial cells(HUVECs)were induced with 0.05 μM doxorubicin for 48 h to establish a stress-triggered premature senescence model.The lentiviral transfection method was employed to achieve DHCR24 overexpression in HUVECs.Cell senescence was evaluated by β-galactosidase staining and Western blot to detect the expression of the senescence-related molecules cyclin-dependent kinase inhibitor 1A(P21)and nicotinamide adenine dinucleotide dependent histone deacetylase 1(SIRT1).Western blot was performed to detect DHCR24 and endothelial nitric oxide synthase(eNOS)expression during endothelial senescence.DAF-FM DA(an NO fluorescent probe)was used to detect intracellular NO production.Results In the stress-triggered premature senescence model of HUVECs induced by doxorubicin,the expression of the senescence marker P21 was up-regulated(t=19.44,P＜0.01),SIRT1 was down-regulated(t=10.10,P＜0.01,and the expression of DHCR24 was down-regulated(t=5.946,P＜0.01),compared with the control group.Meanwhile,eNOS and NO expression was inhibited(t=11.26,P＜0.01;t=10.83,P＜0.01).After DHCR24 overexpression,compared with the control stimulation group,the overexpression stimulation group showed that DHCR24(F=72.10,P＜0.01)was up-regulated.DHCR24 overexpression alleviated the doxorubicin-induced decrease in eNOS and NO(F=5.797,P＜0.05;F=45.12,P＜0.01),compared with the control group.Conclusions DHCR24 may mitigate doxorubicin-induced senescence-related vascular endothelial dysfunction by modulating the eNOS/NO signaling pathway.
维普
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