Ghrelin和下丘脑神经肽Y在2型糖尿病大鼠发病过程中的变化

Pathological changes of ghrelin and hypothalamic neuropeptide Y in rats with type 2 diabetic mellitus

目的观察在2型糖尿病(T2DM)大鼠模型形成过程中ghrelin和下丘脑神经肽Y(NPY)的变化,探讨ghrelin及NPY在T2DM大鼠发病过程中的作用。方法选择SD大鼠60只,分为对照组15只、高脂饮食诱导肥胖(DIO)4周组(DIO 4周组)15只(高脂饮食喂养4周)、DIO 8周组15只(高脂饮食喂养8周)和T2DM组15只。以DIO结合小剂量链脲佐菌素(15mg/kg)法建立T2DM大鼠模型。应用酶联免疫吸附法检测大鼠空腹血浆及胃组织匀浆ghrelin水平;RT-PCR法检测下丘脑NPY mRNA的表达变化。结果与对照组比较,DIO4周组、DIO8周组和T2DM组大鼠血浆和胃组织ghrelin水平明显降低(P<0.01),NPY mRNA表达明显升高[(1.18±0.14)、(1.54±0.09)和(1.82±0.12)vs(0.88±0.17),P<0.01]。NPY mRNA与ghrelin水平呈负相关(r=-0.989,P<0.01)。结论 ghrelin可能通过刺激下丘脑NPY的合成和分泌,共同参与T2DM的形成。

Objective To study the role of ghrelin and hypothalamic neuropeptide Y （NPY） in a rat model of type 2 diabetes mellitus （T2DM） by observing their pathological changes.Methods Sixty SD rats were randomly divided into control group,4-week high fat diet-induced obesity （DIO4） group,8-week high fat diet-induced obesity （DIO8） group and T2DM group （15 in each group）.The animals in DIO4 and DIO8 groups were fed with high fat diet for 4 and 8 weeks,respectively.A rat T2DM model was established by inducing obesity with high fat diet and low streptozotocin dose （15 mg/kg）.Serum levels of fasting ghrecin and gastric ghrelin were measured by ELISA and expression of NPY mRNA in hypothalamus was detected by RT-PCR.Results The serum gastric ghrelin level was significantly lower whereas the NPY mRNA expression level was significantly higher in DIO4 group,DIO8 group and T2DM group than in control group （1.18±0.14 vs 0.88±0.17,1.54±0.09 vs 0.88±0.17,1.82±0.12 vs 0.88±0.17,P＜0.01）.The NPY mRNA expression level was negatively related with the serum ghrelin level （r=-0.989,P＜0.01）.Conclusion Ghrelin is involved in the pathogenesis of T2DM by stimulating the synthesis and secretion of NPY.