| Objective:To study whether glucagon like peptide-1(GLP-1)can increase the expression of ABCA1 and ABCG1 to achieve the reverse transport of cholesterol,reduce the accumulation of cholesterol in macrophages,and ultimately reduce high fat The area of atherosclerotic plaques in reared ApoE-/-mice.methods:Divide 6-8 week-old male ApoE-/-knockout experimental mice into four groups:blank control group(normal rearing),experimental group(high-fat rearing),and GLP-1 excited group(high-fat rearing + GLP-1 drug injection),GLP-1 inhibition group(high-fat feeding + GLP-1 drug injection + Exendin(9-39));ApoE-/-mouse aortic plaques were observed by HE staining and oil red O staining Block area,and observe the expression of ABCA1 and ABCGA by immunohistochemistry;(2)After subculturing RAW264.7 macrophages from mice,they were divided into 8 groups:blank control group,experimental group,different concentrations of GLP-1(0,1.5,3,5,10nmol/L)activation group,GLP-1 inhibition group,and detect the levels of ABCA1,ABCG1 m RNA,protein,TC,FC,CE in each group by PCR,WB,and high performance liquid chromatography.Results:(1)Animal experiment: Compared with the blank control group,the plaque area of the experimental group was significantly increased(P<0.05),and the expression of ABCA1 and ABCG1 was significantly reduced(P<0.05);compared with the experimental group,the plaque area of the GLP-1 excited group was significant Decrease(P<0.05),the expression of ABCA1 and ABCG1 was significantly increased(P<0.05);compared with the GLP-1 activation group,the plaque area of the GLP-1inhibition group was significantly increased(P<0.05),and the expression of ABCA1 and ABCG1 The amount was significantly reduced(P<0.05).(2)Cell experiment: Compared with the blank control group,the expression of ABCA1,ABCG1 m RNA and protein in the experimental group was significantly reduced(P<0.05),and the content of TC,FC,and CE was significantly increased(P<0.05);compared with the experimental group,GLP-1 The expressions of ABCA1,ABCG1 m RNA and protein in the agonistic group were significantly increased(P<0.05),and the contents of TC,FC,and CE were significantly reduced(P<0.05);compared with the GLP-1 agonistic group,the GLP-1 inhibitory group ABCA1,ABCG1 m RNA and The protein expression decreased significantly(P<0.05),and the content of TC,FC,CE increased significantly(P<0.05).Conclusion:(1)At the cellular level: the expression level of ABCA1 and ABCG1 can be significantly increased under the influence of GLP-1,and under the indirect influence of GPL-1,the level of intracellular cholesterol will also decrease,causing macrophages to foam This process of cell transformation is inhibited.(2)At the animal level: GLP-1 can increase the expression of ABCA1 and ABCG1 to a certain extent,thereby reducing the area of aortic plaques in high-fat ApoE-/-mice and realizing the reverse transport of aortic plaques. |
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