GLP-1抑制小鼠主动脉瓣膜钙化的实验研究  

GLP-1 inhibited calcification of the aortic valve in mice

作　　者：胡帅 周景昕 戴亚伟 唐义虎 赵萌 李跞 吴延虎 HU Shuai;ZHOU Jingxing;DAI Yawei;TANG Yihu;ZHAO Meng;LI Luo;WU Yanhu(Department of Cardiovascular Surgery,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China)

机构地区：[1]南京医科大学第一附属医院心脏大血管外科,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2020年第7期950-955,共6页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金(81700340)。

摘　　要：目的:探究胰高血糖素样肽-1(glucagon like peptide-1,GLP-1)对高脂高胆固醇饮食小鼠主动脉瓣钙化的影响,揭示GLP-1在钙化性主动脉瓣疾病(calcified aortic valve disease,CAVD)发生发展中的保护作用及作用机制。方法:SPF级C57BL/6小鼠36只(8周龄,雌性)随机分成4组(n=9),正常饮食组和GLP-1对照组给予正常饮食,高脂饮食组和GLP-1干预组给予高脂高胆固醇+维生素D2饮食,GLP-1对照组和GLP-1干预组在此基础上给予GLP-1处理。12周后,测量各组小鼠二维超声心动图指标,包括主动脉瓣口面积、左室射血分数、瓣叶厚度、左室收缩末内径、跨瓣流速,测定血清钙浓度,von Kossa染色观察瓣膜组织钙化情况,免疫组化法检测各组主动脉瓣标本中骨桥蛋白以及相关信号通路磷酸化p38蛋白的表达水平。结果:①正常饮食组、GLP-1对照组和GLP-1干预组小鼠瓣叶厚度、跨瓣流速、左室收缩末内径及血清钙离子浓度均低于高脂饮食组,而瓣口面积及左室射血分数均高于高脂饮食组(P<0.05);②正常饮食组、GLP-1对照组和GLP-1干预组主动脉瓣膜标本中骨桥蛋白以及相关信号通路磷酸化p38蛋白的表达水平明显低于高脂饮食组(P<0.05)。结论:GLP-1可能通过抑制磷酸化p38蛋白的表达而抑制小鼠主动脉瓣膜的钙化。Objective:To investigate the effect of glucagon like peptide-1(GLP-1)on the calcification of aortic valve in mice fed with high fat and cholesterol diet,and to reveal the protective effect and mechanism of GLP-1 in the occurrence and development of calcified aortic valve disease(CAVD).Methods:Thirty six C57BL/6 mice(8 weeks old,female)were randomly divided into four groups(n=9).The normal diet group and the GLP-1 control group were given normal diet,and the high fat diet group and the GLP-1 intervention group were fed with high fat and high cholesterol diet+vitamin D2.The GLP-1 control group and the GLP-1 intervention group were additionally treated with GLP-1.After 12 weeks,the two-dimensional echocardiographic data of mice in each group were measured,including aortic valve area(AVA),left ventricular ejection fraction(EF),valve leaf thickness(T),left ventricular end systolic diameter(LVDs),transvalvular velocity(TV).Then the serum calcium concentrations were measured,and von Kossa staining was used to observe the calcification of valve tissue,and immunohistochemistry to detect the expression of osteopontin(OPN)and p38 protein in the aortic valve samples.Results:①In the normal diet group,the GLP-1 control group and the GLP-1 intervention group,T,TV,LVDs and serum calcium concentration were lower than those in the high fat diet group,while AVA and left ventricular EF were higher than those in the high fat diet group(P<0.05).②The expressions of OPN and phosphorylated p38(p-p38)in the aortic valve samples of the normal diet group,the GLP-1 control group,the GLP-1 intervention group were significantly lower than that of the high fat diet group(P<0.05).Conclusion:GLP-1 can inhibit the calcification of aortic valve by inhibiting the expression of p-p38 in mice.

关 键 词：胰高血糖素样肽-1 主动脉瓣钙化 动物模型 骨桥蛋白 P-P38 

分 类 号：R542.5[医药卫生—心血管疾病]