Exendin-4对高脂饮食载脂蛋白E基因敲除小鼠脂代谢及炎症因子的影响  

Influences of Exendin-4 on Lipid Metabolism and Inflammation Cytokines in High-Fat Diet Apolipoprotein E Gene Knockout Mice

作　　者：涂强 吴瑞霞[1] 杨勇[1] 谢华[1] 谢华强[1] 陈平英[1] 曹政[1,2] TU qiang;WU Ruixia;YANG Yong;XIE Hua;XIE Huaqiang;CHEN Pingying;CAO Zheng(Taihe Hospital,Hubei University of Medicine,Shiyan,442000,Hubei,China)

机构地区：[1]十堰市太和医院,湖北十堰442000 [2]湖北医药学院,湖北十堰442000

出　　处：《中西医结合心脑血管病杂志》2019年第21期3317-3321,共5页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：2017年国家自然科学基金面上项目(No.81771522);2019湖北省教育厅指导性项目(No.B2019111)

摘　　要：目的观察Exendin-4对高脂饮食载脂蛋白E基因敲除(ApoE^-/-)小鼠脂代谢、白细胞介素-6(IL-6)、单核细胞趋化蛋白-1(MCP-1)及血管内皮细胞黏附分子-1(VCAM-1)表达的影响。方法将40只雄性ApoE^-/-小鼠随机分为普通饮食组(10只)和高脂饮食组(30只),喂养8周后再将高脂饮食组分为非药物干预组、Exendin-4低剂量组、Exendin-4高剂量组,每组10只。Exendin-4低剂量组、Exendin-4高剂量组ApoE^-/-小鼠分别给予20μg/(kg·d)、100μg/(kg·d)Exendin-4腹腔内注射;普通饮食组、非药物干预组ApoE^-/-小鼠给予0.1 mL生理盐水腹腔内注射。第12周末处死小鼠,进行相关检测,采用全自动生化分析仪检测小鼠总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)及高密度脂蛋白胆固醇(HDL-C)水平;RT-PCR及Western Blot法分别检测主动脉IL-6、MCP-1及VCAM-1 mRNA和蛋白表达水平;酶联免疫吸附试验(ELISA)检测血浆中IL-6、MCP-1及VCAM-1水平。结果与普通饮食组相比,非药物干预组ApoE^-/-小鼠TC、LDL-C水平明显升高(P<0.01),应用Exendin-4干预后,Exendin-4高剂量组TC、LDL-C水平明显降低(P<0.05或P<0.01);各组小鼠血清中TG、HDL-C含量虽有变化,但差异无统计学意义(P>0.05)。与非药物干预组相比,Exendin-4处理可以降低主动脉IL-6、MCP-1及VCAM-1 mRNA及蛋白表达,同时下调血浆中IL-6、MCP-1及VCAM-1蛋白水平,差异均有统计学意义(P<0.05或P<0.01)。结论Exendin-4可以改善高脂饮食ApoE^-/-小鼠脂代谢并降低主动脉IL-6、MCP-1及VCAM-1的表达。Objective To observe the effects of Exendin-4 on lipid metabolism and the expression of interleukin-6(IL-6),monocyte chemoattractant protein-1(MCP-1)and vascular cell adhesion molecular-1(VCAM-1)in high-fat diet apolipoprotein E gene knockout(ApoE^-/-)mice.Methods A total of 40 male ApoE^-/- mouse were randomly assigned to normal diet group(n=10)and high-fat diet group(n=30).After eight weeks of feeding,the mice in the high-fat diet group were divided into three groups(n=10):non-drug intervention group,low-dose Exendin-4 group and high-dose Exendin-4 group.ApoE^-/- mice in the low-dose and high-dose exendin-4 groups were given intraperitoneal injections of 20μg/(kg·d)and 100μg/(kg·d)Exendin-4 respectively.At the end of 12th week,all mouse were sacrificed for correlative detection.Total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were determined by an automatic biochemical analyzer.RT-PCR and Western-blot were applied to detect the mRNA and protein expression of IL-6,MCP-1 and VCAM-1 in aortic.The levels of IL-6,MCP-1 and VCAM-1 in serum were measured by enzyme-linked immunosorbent assy.Results The TC and LDL-C in the non-drug intervention group were significantly higher than that in normal diet group(P<0.01),the increased TC and LDL-C levels were significantly reduced after the treatment of Exendin-4(P<0.05 or P<0.01).Although TG and HDL-C levels in the serum of each group changed,the difference was not statistically significant(P>0.05).Compared with data in the non-drug intervention group,the expression of mRNA and protein of IL-6,MCP-1 and VCAM-1 in aortic were significantly decreased after the treatment of Exendin-4,and the levels of IL-6,MCP-1 and VCAM-1 in serum were down-regulated,with statistically significant differences(P<0.05 or P<0.01).Conclusion The Exendin-4 can improve the lipid metabolism of ApoE-/-mice on a high-fat diet and inhibit the expression of IL-6,MCP-1 and VCAM-1 in the aorta.

关 键 词：动脉粥样硬化 EXENDIN-4 白细胞介素-6 单核细胞趋化蛋白-1 血管内皮细胞黏附分子-1 血脂 

分 类 号：R543.5[医药卫生—心血管疾病]