Rg1-R1-PCAD Components Regulates The AMPK/m-TOR Pathway Alleviate The Effect Of Cell Senescence On Atherosclerosis

Objective:To explore the effect of cellular senescence on atherosclerosis.And to investigate the regulatory effects of Ginsenoside Rg1（Rg1）-Notoginsenoside R1（R1）-Protocatechualdehyde PCAD（PCAD）（Rg1-R1-PCAD,RRP）components on the AMPK/m-TOR pathway to reveal the underlying mechanism by which RRP components antagonize atherosclerosis by delaying cellular senescence.Methods:Apo E-/-mice were fed with high-fat diet to replicate atherosclerosis model.RRP component and rosuvastatin were used for intervention treatment.The experiment was divided into Control group（0.9%sodium chloride,intraperitoneally）,Model group（0.9%sodium chloride,intraperitoneally）,ROS group（10 mg/kg-1 rosuvastatin,by gavage）,and RRP group(10 mg/kg Rg1+10 mg/kg R1+14 mg/kg PCAD kg^-1,by intraperitoneal injection).The atherosclerotic plaque area of mouse aortas was determined by oil red O staining,HE staining,and Movat staining;serum total cholesterol（Chol）,triglyceride（TG）,high-density lipoprotein（HDL）,and low-density lipoprotein（LDL）levels were measured using a lipid assay kit;The senescence associated secretory phenotype（SASP）of mouse serum was assessed by Enzyme-linked immunosorbent assay（ELISA）;Senescence associated-β-Galactosidase（SA-β-Gal）staining and immunohistochemistry were used to detect the cellular senescence in mice aorta,and the effects of RRP components on cellular senescence,autophagy levels and AMPK/m-TOR pathway in Apo E^-/-mice were evaluated by Western blot and real-time PCR.Results:The RRP group effectively reduced atherosclerotic plaque area in aortic vessels of Apo E^-/-mice,reduced serum lipid levels,and reduced IL-1βin mouse serumα、IL-1β、IL-6、MMP-3、TNF-α、TGF-β、MCP-1 expression levels and reduced aortic SA-β-Gal andγ-H2AX expression.Real-time PCR and Western blot showed that the RRP group and ROS group were able to reduce p53,p21,and p16 m RNA and protein expression to various degrees,accompanied by AMPK activationα,Suppresses m-TOR expression,thereby regulating autophagy-related protein Becline-1,p62,and LC3 B expression.Conclusion:Cellular senescence is involved in the pathological progression of atherosclerosis,and components of RRP can delay cellular senescence,and its mechanism of action is related to AMPK/m-TOR.The present study confirmed that RRP components delayed cellular senescence,activated autophagy,and regulated the AMPK/m-tor signaling pathway,thus further inhibiting atherosclerosis progression.