EETs对高脂饮食诱导的小鼠肥胖和胰岛素抵抗的作用及其机制  

Effect of EETs on obesity and insulin resistance induced by high-fat diet in mice and its mechanism

作　　者：陈方圆 强华[1] 田刚[1] 白晓君 李娟利[1] 袁祖贻[1] CHEN Fangyuan;QIANG Hua;TIAN Gang;BAI Xiaojun;LI Juanli;YUAN Zuyi(Department of Cardiovascular Medicine,First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China)

机构地区：[1]西安交通大学第一附属医院心血管内科,西安710061

出　　处：《山西医科大学学报》2020年第11期1211-1217,共7页Journal of Shanxi Medical University

基　　金：陕西省科学技术厅社会发展基金资助项目(2019SF-114)。

摘　　要：目的分析环氧-二十碳三烯酸(EETs)对高脂饮食诱导的小鼠肥胖和胰岛素抵抗的作用及其机制。方法80只雄性野生C57BL/6J小鼠,随机分为对照组,模型组,11,12-EET组及14,15-EET组,每组20只。对照组给予普通饮食,其余三组给予高脂饮食诱导胰岛素抵抗模型。11,12-EET和14,15-EET组小鼠分别采用微量泵于餐前注射11,12-EET和14,15-EET,1次/d,持续1个月。实验结束前称取小鼠体质量,留24 h尿液,行胰岛素耐量及葡萄糖耐量试验。处死小鼠,留取血标本、肝脏、骨骼肌、心脏及脂肪。用葡萄糖氧化酶法检测血糖,酶比浊法检测TG及TC,ELISA法检测IL-6、IL-1β、TNF-α及MCP-1,HE染色检测脂肪组织巨噬细胞聚集,real time PCR检测脂肪组织Rapgef3 mRNA表达,Western blot分析脂肪组织EPAC蛋白表达。结果模型组小鼠的体质量、皮下脂肪、内脏脂肪质量、血糖、胰岛素、TG及TC水平高于对照组,而11,12-EET组和14,15-EET组指标低于模型组(P<0.05)。葡萄糖耐量和胰岛素耐量试验中,同时点模型组小鼠的血糖均高于对照组,11,12-EET组和14,15-EET组指标均低于模型组(P<0.05)。对照组小鼠脂肪细胞大小一致;模型组脂肪细胞的大小不一,平均面积较对照组增大;11,12-EET组和14,15-EET组的面积较模型组减小(P<0.05)。模型组小鼠IL-6、IL-1β、TNF-α及MCP-1水平高于对照组,11,12-EET组和14,15-EET组水平则低于模型组(P<0.05)。模型组小鼠的Rapgef3 mRNA及EPAC表达高于对照组,11,12-EET组和14,15-EET组Rapgef3 mRNA及EPAC表达则低于模型组(P<0.05)。结论EETs对高脂饮食诱导的小鼠肥胖和胰岛素抵抗有一定的缓解作用,可能与抑制cAMP-EPAC信号通路、减轻巨噬细胞炎症聚集有关。Objective To explore the effects of epoxy eicosapentaenoic acid(EETs)on obesity and insulin resistance induced by high-fat diet in mice and its possible mechanism.Methods Eighty male wild C57BL/6J mice were randomly divided into control group,model group,11,12-EET group and 14,15-EET group.The mice in model group,11,12-EET group and 14,15-EET group were fed with high fat diet to establish the insulin resistance model.The mice in 11,12-EET group and 14,15-EET group were respectively injected with 11,12-EET and 14,15-EET via micropump before the diet for one month.At the end of the experiment,the body weight of mice were weighed and recorded,and the 24 h urine samples of mice were collected.Insulin tolerance test and glucose tolerance test were carried out.Finally,mice were killed to collect blood samples,liver,skeletal muscle,heart and fat.Glucose oxidase method was used to detect the blood glucose.ELISA was used to detect the levels of TG,TC,IL-6,IL-1β,TNF-αand MCP-1.HE staining was used to detect the macrophagocyte of adipose tissue.Real time PCR was used to determine the level of Rapgef3 mRNA in adipose tissue.Western blot was used to analyze the changes of EPAC protein in adipose tissue of mice.Results Body weight,subcutaneous fat weight,visceral fat weight,blood glucose,insulin,TG and TC in model group were higher than those in control group(P<0.05),while those indexes in 11,12-EET group and 14,15-EET group were lower than those in model group(P<0.05).The blood glucose of mice in model group was higher than that in control group(P<0.05),and the index in 11,12-EET group and 14,15-EET group were lower than that in model group(P<0.05).The size of adipocytes was uniform in control group,but it was different in model group,and the average area of adipocytes in model group was larger than that in control group;the area of adipocytes in 11,12-EET group and 14,15-EET group were smaller than that in model group(P<0.05).The number of macrophages gathered around the adipocytes in model group was more than that in cont

关 键 词：EETS 高脂饮食 肥胖 胰岛素抵抗 小鼠 

分 类 号：R363[医药卫生—病理学]