| Objective:This study aims to verify whether glucagon like peptide-1(GLP-1)can affect atherosclerosis by regulating T cell differentiation,especially Th17 and Treg cells,and clarify the exact mechanism of cardiovascular benefits of GLP-1,so as to provide new ideas for clinical drug development.Methods:Male Apo E-/-mice aged 6-8 weeks were randomly divided into three groups: control group(high-fat feeding+normal saline),GLP-1 group(high-fat feeding+GLP-1 drug),GLP-1inhibition group(high-fat feeding+GLP-1 drug+Exendin(9-39)),12 in each group;After feeding with high-fat diet for 3 months,intraperitoneal injection was carried out according to the experimental group for 1 month;The concentration of GLP-1 in serum,the content of blood lipids in serum,the area of aortic plaque in Apo E-/-mice were observed by ELISA,and the aorta was stained with oil red and HE;Masson staining was used to analyze the content of collagen fibers in plaque;The expression of Th17 and Treg cells in aorta and spleen was observed by immunohistochemistry;Detection of Th17 and Treg cell specific cytokines(IL-17,IL-10,TGF-β)by Western-blotting.The expression level and the expression of cholesterol reverse transport-related proteins(ABCA1,ABCG1,SR-B1).Results:1 Serum concentration of GLP-1RA and its effect on serum cholesterol,triglyceride,low density lipoprotein cholesterol and high density lipoprotein cholesterol in Apo E-/-mice.The serum GLP-1 concentration in GLP-1 group was higher than that in the control group(P<0.05).The concentrations of serum total cholesterol,triglyceride and LDL-C in GLP-1 group were lower than those in control group;HDL-C was higher than other groups(P<0.05).2 GLP-1RA alleviates the development of atherosclerosis in HFD fed Apo E-/-mice.Oil red O staining showed that in Apo E mice fed with HFD and injected with GLP-1,the plaque area of the whole aorta or aortic arch was significantly reduced.GLP-1+Exendin group followed.The quantitative damage of oil red O staining in the whole aorta showed that the percentage of damage in GLP-1 group was significantly lower than that in the control group(P<0.05).In addition,GLP-1RA treatment reduced the percentage of injury in a concentrationdependent manner(P<0.05).3 GLP-1RA improved the plaque stability of Apo E-/-mice fed with HFD.Compared with the control group,the collagen content in the plaque after GLP-1RA treatment increased(P<0.05).4 Effect of GLP-1RA on Th17/Treg balance in spleen and aorta.Compared with the control group,GLP-1RA significantly increased the number of Treg cells in the aorta and spleen,and decreased the infiltration of Th17 cells(P<0.05).5 GLP-1RA up-regulated expression of IL-10,TGF-β;down-regulated IL-17 in the Aorta.The expression level of IL-10 and TGF-β in GLP-1 group was significantly higher than that of the control group,while the expression level of IL-17 was just the opposite(P<0.05).6 GLP-1RA up-regulated RCT regulatory protein in HFD-fed Apo E-/-mice.Compared with the control group,GLP-1RA significantly up-regulated the expression of RCT regulatory proteins ABCA1,ABCG1 and SR-BI in the aorta(P<0.05).Conclusion:As a cardiovascular benefit drug,GLP-1RA improves atherosclerotic plaque area,affects the expression of Th17,Treg cell related cytokines,and upregulates the expression of cholesterol reversal related proteins such as ABCA1,ABCG1,and SR-BI by regulating T cell differentiation. |
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