Effect Of Intermittent Fasting On Atherosclerotic Plaque And Its Mechanism

Background and ObjectiveStroke has become the leading cause of death in China,among which 60%to 80%are ischemic stroke,and atherosclerotic plaque,as the main risk factor of ischemic stroke,has been widely concerned.It is found that the essence of atherosclerosis is a chronic inflammation,which is closely related to the growth of age and aging.However,there are few drugs for the treatment of atherosclerotic plaque,and it is difficult to stick to them for a long time,so it is very important to find a new treatment.Intermittent fasting refers to a periodic way of eating that does not take in calories or very low calorie intake in a period of time,and takes in calories at will in the rest of the time.Because of its convenient operation and easy control,it has been widely used in fasting and other related research.In the past 20 years,studies have found that intermittent fasting can prolong life span,delay aging,improve inflammatory response,and reduce age-related diseases(such as cardiovascular and cerebrovascular diseases).However,there are few studies on the effect of intermittent fasting on atherosclerotic plaque.Therefore,this study aims to explore the effect of intermittent fasting on atherosclerotic plaques and its possible mechanism,so as to seek a new treatment for atherosclerotic plaques.Methods1.Model preparation and detection Taking 70 ApoE(-/-)mice as the research object,12 weeks of high-fat diet was given,and 6 mice were randomly selected.The mouse(AS mouse)model was successfully prepared.2.Group feeding 64 AS mice were randomly divided into 2 groups:intermittent fasting group(IF group):ad libitum feeding group(AL group)was 32:32.In the IF group,8 hours of daily feed was used for daily feeding,16 hours of fasting,and water was freely ingested.The AL group ate food and water freely 24 hours a day.Group feeding for 28 days.3.Body weight,blood glucose and blood ketone body monitoring Each week,8 mice in each group were randomly selected to measure body weight,blood sugar and blood ketone body.Blood was collected by tail trimming,and blood glucose and ketone testers were used to determine blood glucose and blood ketone levels.4.Mouse serum was collected on the 3rd,7th,14th,and 28th days of group feeding.8 mice in each group were randomly selected and 1-2ml blood was taken from the retro-orbital venous plexus by exfoliation..5.Aortic Root Treatment Eight mice from each group that were sacrificed after blood sampling on the 28th day were quickly taken for fixation,dehydration,embedding,and sectioning.6.Detection of blood triglycerides and high-density lipoprotein The serum of 8 mice in each group on the 28th day was used to determine the levels of blood triglycerides and high-density lipoprotein using a microplate reader colorimetric method.7.Observation of Atherosclerotic Plaque on Aortic Roots Aortic root slices of mice were subjected to hematoxylin-eosin staining(HE staining)and pathological changes were observed under a microscope to determine the plaque area.8.Detection of blood interleukin-17 and tumor necrosis factor-?The serum of 8 mice in each group on the 3rd,7th,14th and 28th days was measured by double antibody sandwich method for interleukin-17 and tumor necrosis Factor-a level.9.Observation of MMP-9 expression in the root of aorta Mice aortic root slices were immunohistochemically stained to observe the expression of MMP-9 under a microscope,and the average optical density was measured.Results1.On the 0th,7th,14th,21st,and 28th day of group treatment,there was no significant difference in body weight between the IF group and the AL group(P>0.05).On the 7th,14th,21st,and 28th day of group treatment,the blood glucose level of the IF group was lower than that of the AL group,and the blood ketone body level was increased(P<0.01).2.After 28 days of treatment,the blood triglyceride level of the IF group was lower than that of the AL group,and the blood high-density lipoprotein level was higher than that of the AL group.The differences were statistically significant(P<0.01).3.After 28 days of grouping treatment,the aortic roots in the IF group and the AL group were mostly AS III stage,that is,atherosclerotic plaque stage;the lipid core of the atherosclerotic plaque in the IF group was smaller than that in the AL group,and cholesterol crystals and foam cells Less,and the fiber cap is thicker.The area of atherosclerotic plaque in IF group was lower than that in AL group,the difference was statistically significant(P<0.01).4.On the 3rd,7th,14th,and 28th days of group treatment,the levels of blood interleukin-17 and tumor necrosis factor-? in the IF group were lower than those in the AL group,and the differences were statistically significant(P<0.05).5.After 28 days of grouping treatment,the expression of MMP-9 in aortic plaques in the aortic root of IF group was weaker than that of AL group,and the difference was statistically significant(P<0.05).Conclusions1.Intermittent fasting reduces the area of atherosclerotic plaques in AS mice and delays the formation of atherosclerotic plaques.2.Intermittent fasting changed the energy supply of AS mice from glucose metabolism to fat metabolism,and changed the blood lipid profile of AS mice.3.Intermittent fasting reduces the expression levels of interleukin-17 and tumor necrosis factor-? in AS mice,reduces the inflammation of the blood vessel wall,and delays the atherosclerosis process.In addition,intermittent fasting also reduced the expression of MMP-9 in atherosclerotic plaques of AS mice,which may increase the stability of plaques and reduce the incidence of stroke.