巴西苏木素调控Nrf2/GPX4通路抑制铁死亡治疗动脉粥样硬化的机制研究OA

Objective To investigate the effects of Brazilin(BZ)on atherosclerosis(AS)in rats by regulating the ferroptosis based on Nrf2/GPX4 pathway.Methods A total of forty SD rats were randomly divided into four groups(n=10 per group):control,model,BZ,and Fer-1 groups.The control group was fed a standard diet,while the other groups received a high-fat diet combined with intraperitoneal vitamin D3 injections for 8 weeks to establish the AS model.From week 9,the control and model groups were administered an equivalent volume of normal saline via oral gavage,whereas the BZ and Fer-1 groups were administered BZ[5 mg/(kg·d)]and Fer-1 inhibitor[1 mg/(kg·d)],respectively,for 8 weeks consecutively.Aortic lipid deposition,plaque formation,and endothelial structural damage were assessed using Oil Red O and hematoxylin-eosin(HE)staining.Serum levels of total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)were measured by ELISA.Colorimetric assays were used to quantify ferrous iron(Fe²⁺),malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione(GSH).Western blot was performed to evaluate aortic expression of nuclear factor erythroid 2-related factor 2(Nrf2),glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),and acyl-CoA synthetase long-chain family member 4(ACSL4).Results Compared with the model group,both BZ and Fer-1 groups demonstrated alleviation in aortic lipid deposition,plaque formation,and endothelial structural damage with varying extents,the serum levels of TC,TG,LDL-C,IL-6,IL-1β,and TNF-α were reduced significantly(P<0.01),while serum levels of SOD and GSH were significantly elevated(P<0.01,P<0.05);MDA levels were decreased(P<0.01),and serum Fe2+content was reduced(P<0.01).The expression of ferroptosis-related proteins Nrf2,GPX4,and SLC7A11 was upregulated(P<0.01),whereas ACSL4 expression was downregulated(P<0.01).Conclusion Brazilin attenuates AS in rats,its mechanism my be related to activate the Nrf2/GPX4 pathway and thereby suppressing ferroptosis.