GLP-1通过调节巨噬细胞泡沫化抑制ApoE-/-小鼠动脉粥样硬化的作用机制研究

目的 研究胰高血糖素样肽1(GLP-1)是否能抑制高脂饮食喂养的载脂蛋白E基因敲除(ApoE-/-)小鼠动脉粥样硬化(AS)进程,从巨噬细胞泡沫化角度探讨相关作用机制.方法 选择6周龄雄性ApoE-/-小鼠40只,随机分为对照组(普通饮食)、模型组(高脂饮食)、GLP-1组(高脂饮食+GLP-1)和GLP-1阻断组(高...

GLP-1 regulating macrophage regulates atherosclerosis in ApoE-/-mice Mechanism of GLP-1 inhibition of atherosclerosis in ApoE-/-mice by modulating macrophage foaminess

Objective To investigate the inhibitory effect of glucagon-like peptide 1(GLP-1)on atherosclerosis(AS)process in apolipoprotein E knockout(ApoE-/-)mice with a high-fat diet,and to explore the relevant mechanism from the perspective of macrophage foaming.Methods Forty 6-week-old male ApoE-/-mice were selected and randomly divided into control group(regular diet),model group(high-fat diet),GLP-1 group(high-fat diet+GLP-1),GLP-1 blocking group(high-fat diet+GLP-1+GLP-1 inhibitor)with ten rats in each group.After 12 weeks of feeding,the mice were sacrificed for collection of blood collection,and an automatic biochemical instrument detected the blood lipid level.The aorta root was cut for tissue embedding and slice,observed by HE staining in pathological changes.The foaming status of isolated macrophages was detected by oil red O staining.The expression of leukocyte differentiation antigen 36(CD36)and scavenger receptor A(SR-A)mRNA in macrophages was detected by RT-PCR,and CD36 and SR-A protein expression in the cells was detected by Western blot.Results Compared with the control group,the levels of total cholesterol(TC),triacylglycerol(TG)high-density lipoprotein cholesterol(HDL-C),high-density lipoprotein cholesterol(LDL-C),degree of macrophage foaming as well asCD36,SR-A mRNA,and relative protein expression in macrophage increased significantly in the model group,GLP-1 group and GLP-1 blocking group(P<0.05).Compared with the model group,the levels of serum TC,TG,HDL-C,LDL-C,degree of macrophage foaming,as well asCD36,SR-A mRNA and protein relative expression in macrophage decreased significantly in the GLP-1 group(P<0.05).Compared with the GLP-1 group,TC,TG,HDL-C,LDL-C,degree of macrophage foaming,as well asCD36,SR-A mRNA and protein relative expression in macrophage increased significantly in the GLP-1 blocking group(P<0.05).Conclusion GLP-1 may inhibit the occurrence and development of atherosclerosis in ApoE-/-mice by inhibiting the foaming of macrophages.