Artemisinin Reduces Atherosclerosis In ApoE^-/-diabetic Mice By Inhibiting Ferroptosis Via Activating Nrf2

【Objective】:To investigate the effect of artemisinin（Art）on atherosclerosis（AS）in diabetic mice by inhibiting ferroptosis,and to further clarify the regulatory relationship between Nrf2 pathway and its effect,provide new ideas for improving the mechanism of diabetic atherosclerosis,and add evidence for the pharmacological effect of artemisinin in inhibiting ferroptosis and improving atherosclerosis.【Method】:1.Apo E^-/-Diabetic mouse models were induced by intraperitoneal injection of streptozotocin（STZ）（100 mg/kg）and feeding with a high-fat diet.2.Experimental animals were divided into five groups:control group,diabetic group,artemisinin+diabetic group,artemisinin+ferroptosis inducer+diabetic group,and artemisinin+Nrf2 inhibitor+diabetic group.Elisa was used to measure the expression of Fe²⁺,NADPH,SOD,ROS and MDA in mouse aorta,and Western blot was used to measure the levels of GPX4,Nrf2 and HO-1 in mouse aorta.Aortic strips and aortic sinus plaques were stained with Oil Red O solution for analysis.【Results】:1.Fasting blood glucose≥11.1 mmol/L was considered as a successful diabetic model.2.Compared with the diabetic group,diabetic mice treated with artemisinin had significantly reduced aortic gross and aortic sinus plaque formation,reduced aortic Fe²⁺,ROS and MDA contents,increased SOD and NADPH contents,and increased GPX4,Nrf2,and HO-1 protein expression.3.After mice were treated with the iron death inducer Erastin,and the Nrf2 inhibitor ML385 in combination with artemisinin,Aortic strips and aortic sinus plaque formation was significantly increased compared with artemisinin alone.As well as increased Fe²⁺,ROS and MDA contents,decreased SOD and NADPH contents,and significantly reduced GPX4protein expression.Nrf2 and HO-1 protein expression were slightly decreased after the use of Erastin.After using ML385,Nrf2 and HO-1protein expression was significantly decreased.【Conclusion】:Artemisinin can reduce atherosclerotic lesions in Apo E^-/-diabetic mice by inhibiting ferroptosis by activating Nrf2/HO-1.