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 dia-betic 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 DIO4W group(n=20),DIO8W 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 meas-ured. 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 DIO4W group,DIO8W 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 DIO8W group and type 2 diabetes group were significantly higher than those in DIO4W group(P<0. 05). The concen-trations of serum leptin and hypothalamic NPY in type 2 diabetes group were significantly higher than those in DIO8W group(P<0. 05). There were significant differences in NPY mRNA expression level among normal control group(0. 85 ± 0. 14),DIO4W group(1. 16 ±0. 15),DIO8W 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 DIO4W group,DIO8W group and type 2 diabetes group was significantly higher than that in nor-mal control group,respectively(P<0. 05). NPY mRNA expression level in DIO8W group and type 2 diabetes group was signif-icantly higher than that in DIO4W group,respectively(P<0. 05). NPY mRNA expression level in type 2 diabetes group was significantly higher than that in DIO8W group(P<0. 05). Concentration of serum leptin was positively correlated with concen-tration 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.
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