二甲双胍刺激肝脏瘦素受体基因表达上调血浆可溶性瘦素受体水平

发布时间：2018-05-12 19:42

本文选题：二甲双胍 + 瘦素受体　；参考：《第三军医大学学报》2015年08期

【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(P0.05,P0.01);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。
[Abstract]:Objective to investigate the possible mechanism of metformin upregulating plasma soluble leptin receptor OB-R. Methods 42 healthy male C57BL/6 mice aged 6 and 8 weeks were randomly divided into two groups: normal diet group (n = 21) and high fat diet group (n = 21). After feeding for 5 months, CD group and HF group were randomly divided into 3 subgroups, 7 rats in each group were given distilled water (no control group, metformin 50200 mg/(kg d), their plasma and liver were taken 15 days later. The levels of soluble leptin receptor OB-R17 in plasma of mice were detected by Elisa. Real-time PCR was used to detect the expression of leptin receptor gene OB-RttnOB-RaB-RB-Rd) and the expression of ADAM17 gene in liver by disintegrin and metalloproteinase 10a disintegrin and metalloproteinase 10ADAM10ADAM17 gene. Expression of ADAM10 and ADAM17 protein in renal tissues. Results compared with control group, metformin 200 mg/(kg d in plasma of mice in CD group and HF group were increased after different doses of metformin. Compared with other two groups, metformin 50200 mg/(kg d in HF group was higher than that in control group. The difference was statistically significant. The increase of OB-R level of P0.05 and P0.01 was dose dependent on metformin. Metformin could up-regulate the expression of leptin receptor gene OB-Rt mRNA in the liver in a dose-dependent manner, and the increase of leptin receptor was more obvious in HF group than that in HF group, and the increasing trend of leptin receptor subtype OB-RcC OB-Rd was the same as that of OB-Rt. There was no significant change in the expression of leptin receptor gene OB-RtnnOB-RaB-Rab, OB-RbCU OB-RcOB-Rd between metformin group and control group. There was no significant difference between CD group and HF group. There was no significant change in the expression of ADAM17 in liver and kidney tissues between CD group and HF group, metformin group and control group. Conclusion Metformin can significantly up-regulate the level of plasma s OB-R by stimulating the expression of leptin receptor gene in the liver. The main source of metformin is the short leptin receptor of the liver.
【作者单位】：第三军医大学新桥医院内分泌科;第三军医大学新桥医院中西医结合科;第三军医大学基础医学部生物化学与分子生物学教研室;
【基金】：国家自然科学基金面上项目(30971082,81270482)~~
【分类号】：R965

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