阿必鲁肽调节2型糖尿病大鼠糖脂代谢及下丘脑SOCS-3、NF-κBmRNA表达水平

Effect of Albiglutide on Glycolipid Metabolism and Expression of SOCS-3 and NF-κB mRNA in the Hypothalamus of Type 2 Diabetic Rats

目的:观察阿必鲁肽对2型糖尿病(T2DM)大鼠糖脂代谢和下丘脑组织细胞因子信号转导抑制蛋白-3(SOCS-3)、核因子Kappa B(NF-κB)mRNA表达的影响。方法:40只SD雄性大鼠适应性饲养1周后,随机选择30只并一次性腹腔注射小剂量链脲佐菌素(STZ,30mg/kg),并给予高糖高脂饲料饲养1周造模。成模大鼠随机平分为T2DM组、阳性对照药物利拉鲁肽组(利拉鲁肽组)及观察药物阿必鲁肽组(阿必鲁肽组)。未经处理的10只大鼠为正常对照组。观察各组大鼠空腹血糖(FBG)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDLC)和高密度脂蛋白胆固醇(HDL-C)及下丘脑SOCS-3、NF-κB mRNA表达水平变化。结果:与正常对照组比较,T2DM组、利拉鲁肽组及阿必鲁肽组FBG、TC、TG、LDL-C明显升高,HDL-C明显降低(P<0.05或P<0.01)。利拉鲁肽组及阿必鲁肽组FBG、TG和LDL-C水平均较T2DM组降低,阿必鲁肽组降低更明显(P<0.05),但HDL-C水平变化不明显(P>0.05)。T2DM组大鼠下丘脑SOCS-3、NF-κB mRNA表达水平均较正常对照组明显升高(P<0.05),利拉鲁肽组及阿必鲁肽组SOCS-3、NF-κB mRNA表达水平均较T2DM组显著下降(P<0.01),且阿必鲁肽组下降更明显(P<0.01)。结论:阿必鲁肽可降低T2DM大鼠血糖、血脂水平,其作用机制可能与其调节下丘脑SOCS-3、NF-κB mRNA表达有关。

Objective： To observe the effect of albiglutide on glucose and lipid metabolism and hypothalamic tissue cytokine signal transduction inhibitory protein-3 （SOCS-3） and nuclear transcription factor kappa B （NF-κB） mRNA in type 2 diabetes mellitus （T2DM） rats. Method： 40 SD male rats were adapted for 1 weeks, randomly selected 30 with high glucose and high fat diet for 1 weeks and intraperitoneal injection of small dose of streptozotocin （STZ, 30mg/kg） model, the rats were randomly divided into T2DM group, the positive control drug liraglutide group and the drug albiglutide group. The untreated 10 rats were the normal control group. The changes of fasting plasma glucose （FBG）, total cholesterol （TC）, triglyceride （TG）, low density lipoprotein cholesterol （LDL-C）, high-density lipoprotein cholesterol （HDL-C） and SOCS-3 and NF-κB mRNA level in the rats of each group were observed. Results： FBG and TC,TG and LDL-C in T2DM group, liraglutide group and albiglutide group of were significantly higher than the normal control group, HDL-C was significantly lower than the normal control group （ P 〈0.05 or P 〈0.01）. FBG, TG and LDL-C levels in liraglutide and albiglutide group were lower than that in T2DM group, albiglutide group decreased significantly （ P 〈0.05）, but the HDL-C level did not change significantly （ P 〉0.05）. The expression of SOCS-3 and NF-κB mRNA in T2DM group was significantly higher than that in normal control group （ P 〈0.05）. The expressions of SOCS-3 and NF-κB mRNA in liraglutide group and albiglutide group were significantly lower than those in T2DM group （ P 〉0.05）, and albiglutide group was significantly lower than liraglutide group （ P 〈0.01）. Conclusion： albiglutide can reduce the level of blood glucose and blood lipid in T2DM rats, which may be related to the regulation of SOCS-3 and NF-κB mRNA in hypothalamus.