摘要
目的探讨胰高血糖素样肽1(GLP-1)受体激动剂exendin-4影响亲环蛋白A(CyPA)分泌抑制小鼠动脉粥样硬化(AS)及血管钙化过程的作用。方法将20只ApoE^(-/-)小鼠随机分为模型组和exendin-4组,每组10只,高脂饲料喂养建立AS模型,另取10只野生型C57BL/6J小鼠作为对照组,exendin-4组腹腔注射GLP-1R激动剂exendin-4,1次/d,持续8周。8周后,ELISA法测定甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白-胆固醇(HDL-C)、低密度脂蛋白-胆固醇(LDL-C)、CyPA表达水平,甲基麝香草酚蓝比色法检测血清钙水平,油红O染色检测主动脉粥样硬化斑块,HE染色观察主动脉病理学变化,Von Kossa染色观察主动脉钙盐沉积,免疫组织化学、Real-time PCR及Western blotting检测主动脉Runt相关转录因子2(RUNX2)与骨形态发生蛋白2(BMP-2)表达水平,免疫荧光染色检测主动脉CyPA表达。结果与对照组比较,模型组小鼠血清中TG、TC、LDL-C、Ca、CyPA水平升高(P<0.05),主动脉粥样硬化斑块面积均增加(P<0.05),主动脉壁明显增厚且出现大量炎性细胞浸润及钙盐沉积,主动脉组织RUNX2与BMP-2的mRNA及蛋白表达水平均升高(P<0.05),主动脉组织内CyPA表达增强。与模型组比较,exendin-4组小鼠血清中TG、TC、LDL-C、Ca、CyPA水平降低(P<0.05),主动脉粥样硬化斑块面积均减少(P<0.05),主动脉壁增厚与炎性细胞浸润现象明显改善,钙盐沉积减少,主动脉组织RUNX2与BMP-2的mRNA及蛋白表达水平均降低(P<0.05),同时,主动脉组织内CyPA表达减弱。结论GLP-1受体激动剂exendin-4能够抑制小鼠动脉粥样硬化及血管钙化,其机制可能与减少CyPA的分泌相关。
Objective To investigate the effect of glucagon-like peptide 1(GLP-1)receptor agonists exendin-4 on the secretion of cyclophilin A(CyPA)to inhibit atherosclerosis(AS)and vascular calcification in mice role of the process.Methods Twenty ApoE^(-/-)mice were randomly divided into model group and exendin-4 group,10 mice in each group,and were fed with high-fat diet to establish AS model,another 10 wild-type C57BL/6J mice were taken as the control group,and the exendin-4 group was intraperitoneally injected with the GLP-1R agonist exendin-4,1/d,for 8 weeks.After 8 weeks,the ELISA method was used to determine the level of triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)and CyPA,serum calcium level was detected by methylthymol blue colorimetric method,oil red O staining to detect the development of atherosclerotic plaques in the aorta,HE staining was used to observe the pathological changes of the aorta,Von Kossa staining was used to observe the calcium deposition in the aorta,immunohistochemical staining,Real-time PCR and Western blotting were used to detect the expression levels of aortic RUNX2 and bone morphogenetic protein 2(BMP-2),immunofluorescent staining was used to detect the positive expression of CyPA in aortic tissue.Results Compared with the control group,the serum levels of TG,TC,LDL-C,Ca and CyPA in the model group increased(P<0.05),the atherosclerotic plaque areas of the aorta increased(P<0.05),the aortic wall was thickened significantly and a large number of inflammatory cells were infiltrated,a large amount of calcium deposits were deposited in the aortic parietal membrane,the positive expression area ratio of RUNX2 and BMP-2,the relative mRNA expression of RUNX2 and BMP-2,the relative protein expression of RUNX2 and BMP-2 in aortic tissue all increased(P<0.05),and the red fluorescence of CyPA expression in aortic tissue was enhanced significantly.Compared with the model group,the serum levels of TG,TC,LDL-C,Ca and CyPA in the
作者
杨珊珊
潘宇翔
郑婉
王政
YANG Shan-shan;PAN Yu-xiang;ZHENG Wan;WANG Zheng(The Second Department of Cardiovascular Internal Medicine,the First Affiliated Hospital of Hainan Medical College,Haikou 570102,China;Zone 1,Department of Critical Care Medicine,the Second Affiliated Hospital of Hainan Medical College,Haikou 570311,China)
出处
《解剖学报》
CAS
CSCD
2024年第2期229-236,共8页
Acta Anatomica Sinica
基金
海南省卫生健康行业科研项目(20A200179)。
