Study On The Mechanism Of Homoplantaginin And Its Derivatives In Inhibiting Endothelial Cell Apoptosis And Atherosclerosis

Atherosclerosis(AS)is the main cause of coronary heart disease,cerebral infarction,and peripheral vascular disease.Lipid metabolism disorder is the basis of atherosclerosis.The characteristic is that the disease of the affected artery starts from the intima.Generally,the accumulation of lipids,hemorrhage,and thrombosis are preceded by fibrous tissue proliferation and calcium deposition,and there is a mid-arterial layer.The gradual decay and calcification of the artery lead to thickening and hardening of the arterial wall and narrowing of the vascular lumen.The lesions often involve the muscular arteries of the major and middle muscles.Once they develop enough to block the arterial lumen,the tissues or organs supplied by the arteries will be ischemic or necrotic.Because the lipids that accumulate in the arterial intima are yellowish atherosclerotic,it is called atherosclerosis.Vascular endothelial cells(VECs)usually refer to a single layer of flat epithelium lining the inner surface of the heart,blood vessels and lymphatic vessels,also called endothelial cells.Vascular endothelial cell damage is involved in the occurrence and development of atherosclerosis.As a promoting factor of atherosclerosis,ox-LDL(Oxidized low density lipoprotein,ox-LDL)inducing apoptosis of vascular endothelial cells is the first step in the development of atherosclerosis.Therefore,inhibiting vascular endothelial cell apoptosis and stabilizing atherosclerosis is an effective strategy for the treatment of cardiovascular and cerebrovascular diseases.Homoplantaginin are extracted from lychee grass,a plant belonging to the sage genus Labiatae,and belong to flavonoids.Its research has shown that it can relieve cough and relieve asthma,treat liver damage,improve endothelial insulin resistance,inhibit tumor growth,and resist osteoporosis.Induces apoptosis of cancer cells and inhibits various activities such as α-glycosidase.However,the effect of homoplantaginin on endothelial cell apoptosis and atherosclerosis is still unclear.On this basis,we used human umbilical vein endothelial cells and Apo E-/-mice as cell and animal experimental models to study the effects of homoplantaginin and its derivatives(S1,S3)on blood vessels induced by ox-LDL in vitro and in vivo.The role and mechanism of endothelial cell apoptosis and the occurrence and development of atherosclerosis.The results of in vitro experiments showed that S1 and S3 significantly inhibited the apoptosis of vascular endothelial cells induced by ox-LDL through brightfield observation,Hoechst 33258 staining,and TUNEL staining;Western Blot method and DCFH-DA probe method were used to explore S1 and S3 significantly Inhibit the expression of adhesion factors and the accumulation of ROS in cells.The results of in vivo experiments showed that compared with the control group,S1 and S3 significantly reduced the apoptosis rate of aortic sinus endothelial cells by immunotissue fluorescence staining.At the same time,S1 and S3 were investigated by HE,Masson,and Oil Red O staining methods.S3 inhibits the development of atherosclerosis.Mechanism studies have shown that S1 and S3 activate the Nrf2/HO-1 antioxidant pathway in endothelial cells through firefly luciferase report detection.Small interference experiments show that down-regulation of Nrf2 in vitro significantly inhibits the protective effect of S1 and S3 on endothelial cells,and it weakens after si Nrf2 S1 and S3 protect endothelial cell apoptosis,the production of intracellular reactive oxygen species,the expression of adhesion factors and the nucleation of NF-κB.The results of the study revealed the role of homoplantaginin compounds in protecting endothelial cells and inhibiting atherosclerosis,providing new candidate compounds for the treatment of atherosclerosis.