中文摘要：

目的探讨二甲双胍上调血浆可溶性瘦素受体（soluble leptin receptor,s OB-R）的可能机制。方法 42只6-8周龄健康雄性C57BL/6小鼠,按随机数字表法分为正常饮食（CD）组（n=21）及高脂饮食（HF）组（n=21）。喂养5月后,CD组及HF组分别再随机分为3个亚组,每组7只,分别予蒸馏水（不用药对照组）,二甲双胍50、200 mg/（kg·d）灌胃,灌胃15 d后取其血浆及肝、肾组织。ELISA法检测小鼠血浆可溶性瘦素受体（soluble leptin receptor,s OB-R）水平,Real-time PCR检测肝、肾脏组织中瘦素受体基因（OB-Rt、OB-Ra、OB-Rb、OB-Rc、OB-Rd）及解聚素样金属蛋白酶10（a disintegrin and metalloproteinase 10,ADAM10）、ADAM17基因的表达,Western blot检测肝、肾脏组织中ADAM10、ADAM17蛋白的表达。结果与不用药对照组比较,给予不同剂量的二甲双胍后均能升高CD组和HF组小鼠血浆s OB-R,CD组中二甲双胍200 mg/（kg·d）组与其他2组比较,HF组中二甲双胍50、200 mg/（kg·d）组与不用药对照组比较,差异有统计学意义（P〈0.05,P〈0.01）;s OB-R水平升高具有二甲双胍剂量依赖性效应。二甲双胍能上调肝脏瘦素受体基因OB-Rt mRNA的表达,并呈剂量依赖性升高,HF组瘦素受体上升更为明显;瘦素受体亚型OB-Ra、OB-Rc、OB-Rd的上升趋势与OB-Rt趋势一致。肾脏组织中,瘦素受体基因OB-Rt、OB-Ra、OB-Rb、OB-Rc、OB-Rd的表达水平在二甲双胍用药组及不用药对照组相比没有显著变化,CD组与HF组之间也没有显著差异。肝脏和肾脏组织中ADAM10、ADAM17表达量在CD组与HF组、二甲双胍用药组及不用药对照组之间均无显著改变。结论二甲双胍能显著上调血浆s OB-R水平,该作用主要是通过刺激肝脏瘦素受体基因表达实现的,最主要的来源是肝脏的短型瘦素受体。

英文摘要：

Objective To explore the possible mechanism of metformin in up-regulation of serum soluble leptin receptor（ s OB-R） in mice. Methods Forty-two C57 BL /6 mice,aged from 6 to 8 weeks,with normal body weight（ 17. 02 ± 1. 91 g） were randomly divided into 2 groups,which were fed with standard chow diet（ CD）（ n = 21） and high-fat diet（ HF）（ n = 21）,respectively,for 5 months. The mice in each group were then divided into 3 subgroups（ n = 7） and administrated with water,metformin 50 mg /（ kg·d）and metformin 200 mg /（ kg·d）,respectively,via gastric lavage once a day for 15 d. Serum s OB-R was determined by ELISA. Expressions of total leptin receptor（ OB-Rt） and major membrane-bound leptin receptor isoforms（ OB-Ra,OB-Rb,OB-Rc,and OB-Rd） in liver and kidney of the mice were determined by real-time PCR. The expression of A Disintegrin And Metalloproteinase 10（ ADAM10） and ADAM17,which participated in ectodomain shedding of leptin receptor,was detected by real-time PCR and Western blotting.Results After metformin treatment,serum s OB-R levels were increased in both CD group and HF group in a dose-dependent manner,for a more detailed,serum s OB-R levels were increased in metformin 200 mg /（ kg·d）subgroup compared with the other 2 subgroups in CD group（ P〈0. 05）,while they were increased significantly in 2 metformin treatment subgroups compared to non-treatment subgroup in HF group（ P〈0. 01）.Moreover,compared with the non-treatment mice,the expression of OB-Rt mRNA in the liver was dosedependently up-regulated in the metformine-treated mice of the CD group as well as the HF group,and the expression in the HF group was increased more significantly,by the way,the trend was very similar to the level of s OB-R. The OB-Ra,OB-Rc and OB-Rd had the same increase trend as OB-Rt in the liver,but not in kidney. Meanwhile,Adam10 and Adam17 mRNA and protein levels were not significantly changed in both liver and kidney tissues of the CD and HF groups with metformin treatmen