GLP-1(7-36)inhibited The Formation Of Atherosclerotic Plaques In The Aorta Of ApoE-/-mice And Its Effects On The Expression Of CD36 And ACAT1 In Foam Cells

Objective:To investigate the effect of GLP-1 on the formation of atherosclerotic plaques in ApoE-/-mice fed a high-fat diet and the possible targets of its related effects,and to further explore the effect of GLP-1 on the expression of CD36 and ACAT1 in macrophage-derived foam cells,so as to explore the mechanism of its anti-atherosclerotic effects.Methods:(1)18 to 20 g of male ApoE knockout mice aged 6-8 weeks were divided into 4 groups : normal diet group,high fat diet group,GLP-1(7-36)group,GLP-1(7-36)+ Exendin(9-39)group.HE staining and oil red O staining were used to clarify the effect of glp-1 on the plaque area of As in mice.Immunohistochemical staining of CD36 and ACAT1 antibody was used to elucidate the mechanism of the anti-as effect of glp-1.(2)Macrophage experiments were divided into 8 groups : blank control group,foam cell group,different concentrations of GLP-1(7-36)group,GLP-1(7-36)+ Exendin(9-39)group.RT-PCR was used to detect the relative expression of CD36 and ACAT1 mRNA in each group of cells;WB method was used to detect the relative expression of CD36 and ACAT1 protein in each group of cells;and Cholesterol(FC)and total cholesterol(TC)content,and then calculate the cholesterol ester(CE)content;CD36,ACAT1 receptor protein expression was analyzed by cellular immunofluorescence.Results:(1)HE and oil red O staining results showed that the plaque area in the high-fat diet group accounted for(30.3±3.8)% of the aortic intima area.The percentage of plaque area in the aortic intima in the GLP-1 group was(15.1±4.3)%.Compared with the high-fat diet group,the aortic plaque in the GLP-1 group was significantly reduced(P < 0.05).The percentage of the plaque area in the GLP-1 +Exendin group to the intimal area of the aorta was 25.7±3.4 %,which was significantly higher than that in the GLP-1 group(P < 0.05).Glp-1(7-36)decreased the expression levels of CD36 and ACAT1 positive cells in aorta of mice(P < 0.05).Compared with the blank control group,the expression levels of CD36 and ACAT1 mRNA in the foam cell group were higher(P < 0.05);(2)Compared with the foam cell group,the expression levels of CD36 and ACAT1 mRNA in GLP-1 group were significantly decreased(P < 0.05).Compared with GLP-1 group,the expression levels of CD36 and ACAT1 mRNA in GLP-1 +Exendin group were higher(P < 0.05).Compared with the blank control group,the expression levels of CD36 and ACAT1 were higher in the foam cell group(P < 0.05).Compared with the foam cell group,the expression levels of CD36 and ACAT1 in GLP-1 group were relatively low(P < 0.05).Compared with GLP-1 group,the expression levels of CD36 and ACAT1 in GLP-1 +Exendin group were relatively high(P < 0.05).Conclusion:(1)in animal experiments,GLP-1 ApoE-/-mice As plaque formation,reduce the As plaque area,elucidate that GLP-1 inhibited the relative expression of CD36 and ACAT1 in the aorta of ApoE-/-mice,thereby reducing the process of cholesterol inflow and synthesis in the aorta,and reducing the formation of lipid plaques on the vascular wall;(2)Further in the cell experiment,it is clear that GLP-1 can inhibit the development of As plaques by affecting the relative expression of CD36 and the mRNA and protein of ACAT1 in macrophage-derived foam cells,and by down-regulating the accumulation of cholesterol in the intracellular microenvironment,thereby inhibiting the foaming of macrophage-derived foam cells.