麝香通心滴丸通过调控NRF2/GPX4通路抑制铁死亡改善动脉粥样硬化OA

Objective Shexiang Tongxin Dropping Pills is a commonly used drug for the treatment of atherosclerosis(AS).This study aims to investigate the mechanism of Shexiang Tongxin Dropping Pills in the treatment of AS.Methods In this study,ApoE-/-mice were subjected to high-fat feeding to establish AS models.The AS models were randomized into the Control group,Model group,positive drug(PC)group,and low/medium/high-dose Shexiang Tongxin Dropping Pills(STDP-L/M/H)groups.The therapeutic effect of Shexiang Tongxin Dropping Pills on AS mice was verified by detecting the serum profiles of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C),as well as by observing oil red O staining of aortic tissues.The effects of Shexiang Tongxin Dropping Pills on oxidative stress in AS mice were assessed by measuring aortic superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)activities,and malondialdehyde(MDA)levels with commercial biochemical kits.The effect on inflammation in AS mice was assessed by detecting the expression levels of interleukin-6(IL-6),interleukin-1 β(IL-1 β),and tumor necrosis factor-α(TNF-α)in the aorta via ELISA kits.Additionally,the effects on ferroptosis and the NRF2/GPX4 pathway in AS mice were investigated by detecting the expression levels of related proteins using RT-qPCR and Western blot.Results The result showed that Shexiang Tongxin Dropping Pills reduced the serum levels of TC,TG,and LDL-C(P＜0.01),increased the serum level of HDL-C(P＜0.01),alleviated aortic plaque deposition,enhanced the activities of SOD and GSH-Px in the aorta(P＜0.01),decreased the MDA level(P＜0.05),and lowered the levels of IL-6,IL-1β,and TNF-α in AS mice(P＜0.01).Meanwhile,Shexiang Tongxin Dropping Pills regulated the expression of ferroptosis-related proteins(FTL,Transferrin,Steap3,P＜0.05,P＜0.01)and proteins associated with the NRF2/GPX4 pathway(NRF2,GPX4,HO-1,ACSL4,P＜0.05,P＜0.01).Conclusions This study demonstrates that Shexiang Tongxin Dropping Pills can improve atherosclerosis by regulating the NRF2/GPX4 pathway,inhibiting ferroptosis,and suppressing oxidative stress and inflammatory responses.