瘦素-下丘脑神经肽Y轴在2型糖尿病大鼠发病过程中的变化

Changes of Leptin-hypothalamic Neuropeptide Y Axis during the Development of Type 2 Diabetes in Rats

目的观察在2型糖尿病大鼠模型形成过程中,瘦素、下丘脑神经肽Y（NPY）水平的变化。方法选用清洁级180～220 g雄性SD大鼠110只。应用小剂量链脲佐菌素（15 mg/kg）腹腔注射,建立2型糖尿病大鼠模型。采用随机数字表法抽取20只作为正常对照组,喂以基础饲料;90只喂以高脂饮食诱导肥胖（DIO）后,根据模型形成过程中时间点的不同将其分为DIO4W组（20只）、DIO8W组（20只）、2型糖尿病组（20只）。检测4组大鼠空腹血清瘦素水平、下丘脑NPY水平及下丘脑NPY mRNA的表达。结果 4组空腹血清瘦素水平和下丘脑NPY水平比较,差异均有统计学意义（P〈0.05）。DIO4W组、DIO8W组、2型糖尿病组空腹血清瘦素水平和下丘脑NPY水平均高于正常对照组（P〈0.05）;DIO8W组、2型糖尿病组空腹血清瘦素水平和下丘脑NPY水平均高于DIO4W组（P〈0.05）;2型糖尿病组空腹血清瘦素水平和下丘脑NPY水平高于DIO8W组（P〈0.05）。正常对照组、DIO4W组、DIO8W组、2型糖尿病组的NPY mRNA表达水平分别为（0.85±0.14）、（1.16±0.15）、（1.53±0.14）、（1.79±0.13）,差异有统计学意义（F=173.320,P〈0.05）。DIO4W组、DIO8W组、2型糖尿病组的NPY mRNA表达水平均高于正常对照组（P〈0.05）;DIO8W组、2型糖尿病组的NPY mRNA表达水平均高于DIO4W组（P〈0.05）;2型糖尿病组的NPY mRNA表达水平高于DIO8W组（P〈0.05）。4组大鼠空腹血清瘦素水平与下丘脑NPY水平、NPY mRNA表达水平均呈正相关（r=0.951、0.953,P〈0.05）。结论随着2型糖尿病动物模型的形成,大鼠空腹血清瘦素水平升高;下丘脑NPY水平、NPY mRNA表达水平升高,与瘦素水平呈正相关,为进一步研究糖尿病发病机制提供了依据。

Objective To investigate the changes of the serum leptin and hypothalamic neuropeptide Y（ NPY） levels during the development of type 2 diabetes in rats. Methods Selection of clean grade 180- 220 g male SD rats 110. Type 2 diabetic rat models were established by the intraperitoneal injection of low- dose streptozotocin（ 15 mg / kg）. Random number table to extract 20 as the normal control group fed the basal diet. The 90 diet- induced obese（ DIO） rats were divided into DIO4 W group（ n = 20）,DIO8 W group（ n = 20）,and type 2 diabetes group（ n = 20） according to the timing of the development of model. The concentrations of serum leptin, hypothalamic NPY and the expression of hypothalamic NPY mRNA were measured. Results There were significant differences in concentrations of serum leptin and hypothalamic NPY in the four groups（ P〈0. 05）. The concentrations of serum leptin and hypothalamic NPY in DIO4 W group,DIO8 W group and type 2 diabetes group were significantly higher than those in normal control group（ P〈0. 05）. The concentrations of serum leptin and hypothalamic NPY in DIO8 W group and type 2 diabetes group were significantly higher than those in DIO4 W group（ P〈0. 05）. The concentrations of serum leptin and hypothalamic NPY in type 2 diabetes group were significantly higher than those in DIO8 W group（ P〈0. 05）. There were significant differences in NPY mRNA expression level among normal control group（ 0. 85 ± 0. 14）,DIO4 W group（ 1. 16 ± 0. 15）,DIO8 W group（ 1. 53 ± 0. 14） and type 2 diabetes group（ 1. 79 ± 0. 13）（ F = 173. 320,P〈0. 05）.NPY mRNA expression level in DIO4 W group,DIO8 W group and type 2 diabetes group was significantly higher than that in normal control group,respectively（ P〈0. 05）. NPY mRNA expression level in DIO8 W group and type 2 diabetes group was significantly higher than that in DIO4 W group,respectively（ P〈0. 05）. NPY mRNA expression level in type 2 diabetes group was significantly higher than that in DIO8 W group（ P〈0. 05）. Concentration of serum leptin was positively correlated with concentration of hypothalamic NPY and NPY mRNA expression level,respectively（ r = 0. 951,0. 953,P〈0. 05）. Conclusion The levels of serum leptin and hypothalamic NPY,and NPY mRNA expression level increase with the development of type 2 diabetes model. Concentration of serum leptin is positively correlated with concentration of hypothalamic NPY and NPY mRNA expression level,respectively. The findings may provide evidence for Type 2 diabetes pathogenesis research.