The Effect And Mechanism Research Of Puerarin On Angiotensin Ⅱ-induced Abdominal Aortic Aneurysm Formation

Background:Abdominal aortic aneurysm(AAA)refers to the limitations of the abdominal aorta or diffuse tumor-like expansion,in the event of aneurysm rupture,the mortality rate as high as 78-94%.At present,for the diameter of<5.5cm,slow expansion,the recent risk of rupture of the asymptomatic small abdominal aortic aneurysm,there is no clear intervention.But with the patient’s age,the tolerance for surgery gradually decreased,While the aneurysm growth and expansion is irreversible,will inevitably lead to increased risk of surgical treatment after the elderly.For such patients,the current clinical role drugs is limited.Therefore,the development of the pathogenesis of abdominal aortic aneurysm drugs on the prevention and treatment of disease is of great significance.Angiotensinll(Ang Ⅱ)plays an important role in the development and progression of abdominal aortic aneurysm.Mainly through the activation of downstream signaling pathways,induced oxygen free radical production,smooth muscle cell apoptosis,inflammatory factor expression and matrix metalloproteinase synthesis,thereby increasing the abdominal aortic wall of the inflammatory response to accelerate the elastic fibers,collagen degradation and arterial Of the necrosis,arterial wall remodeling,resulting in the gradual expansion of the aneurysm..Puerarin is a highly effective oxygen free radical scavenger,clinically widely used to prevent thromboembolic disease.At present,puerarin has antioxidant free radical damage,cell protection,inhibition of vascular endothelial cell tissue expression,antioxidant and other effects.But whether it can affect the formation of abdominal aortic aneurysm has no literature.Therefore,it is hoped that by studying the effect of puerarin on abdominal aortic aneurysm and the related molecular biological mechanism,it will provide some new ideas for the prevention and treatment of abdominal aortic aneurysmObjective:The main lesions of abdominal aortic aneurysm are the membrane and the outer membrane.From the previous research reports,the pathogenesis of AAA mainly includes oxidative stress,inflammatory reaction,matrix elastic fiber damage and the apoptosis of the middle membrane smooth muscle.If we can develop new drugs for these pathogenesis,we will greatly improve the progress of AAA drug treatment,and at the same time,it is very good to prevent the occurrence and development of AAA.Puerarin is the main component of the traditional Chinese medicine puerarin,clinically used to prevent thromboembolic disease.Puerarin has anti oxygen free radical damage,cell protection,inhibition of vascular endothelial cell tissue factor expression,antioxidant and other functions.But whether it can affect the formation of abdominal aortic aneurysm has not been reported in the literature.Methods:We divided the experimental animals into negative control group,ⅡAng model group(positive control group),100mg/kg Puerarin Treatment group,200mg/kg Puerarin Treatment group.4 weeks after AngⅡ stimulation,the incidence of abdominal aortic aneurysm,NADPH oxidase activity,MMPs activation,ROS production,AP-1 and p-Jun protein expression were detected in four groups.At the same time,the effect of Puerarin on the proliferation and apoptosis of EOMA cells was studied,and the activity of caspase-9/3 in EOMA cells was detected.Result:The results showed that the incidence of abdominal aortic aneurysm in the Ang Ⅱ model group was 80%,while the 200mg/kg and 100mg/kg puerarin treatment groups were reduced to 50%and 30%,respectively.The NADPH oxidase activity,MMPs,The expression of ROS,AP-1 and p-Jun protein was significantly lower than that of Ang Ⅱ model group.At the same time,puerarin significantly inhibited the proliferation of EOMA cells and induced apoptosis,and significantly increased the expression of caspase-9/3 enzyme activity,suggesting that it can promote endothelial cell apoptosis,inhibition of neovascularization.Conclusions:Puerarin can significantly inhibit Ang Ⅱ-induced abdominal aortic aneurysm formation.The possible mechanisms include inhibition of ROS products,decreased expression of matrix metalloproteinases and activity,decreased AP-1 protein expression in aortic aneurysms,reduced p-Jun protein expression,inhibited neovascular endothelial cell proliferation,promoted endothelial cell apoptosis Death,inhibition of intracellular caspase 9/3 enzyme activity.But its specific mechanism needs further study.