摘要
目的：探讨下丘脑神经肽NUCB2与Tsumura Suzuki（TS）多基因突变2型糖尿病（T2DM）小鼠摄食过多的关系。方法：将动物分为Tsumura Suzuki糖尿病（TSD）小鼠、正常小鼠;监视器监测小鼠摄食量;分析血生化指标;定量RT-PCR分析摄食相关神经肽m RNA表达水平;放射免疫分析法检测nesfatin-1蛋白水平。结果：与年龄匹配的TSN小鼠相比,TSD小鼠在1月龄就存在体重增加（P〈0.05）和高瘦素血症（P〈0.05）,3-12月龄出现贪食（P〈0.05）、高血糖（P〈0.05）、高血脂（P〈0.05）和高胰岛素血症（P〈0.05）,且3-12月龄时厌食肽nesfatin-1前体核连蛋白2（NUCB2）m RNA和nesfatin-1蛋白水平均显著降低（P〈0.05~0.01）;TSD小鼠下丘脑甘丙肽、黑色素浓集素、神经肽Y及前黑素细胞皮质素原m RNA水平也有显著改变（P〈0.05）。结论：下丘脑NUCB2介导信号通路破坏可能导致TSD小鼠摄食过多。
Objective： To discuss the relationship between hypothalamic neuropeptide NUCB2 and hyperphagic feeding in Tsumura Suzuki Diabetes（TSD） mice, a model of type 2 diabetes with polygenic abnormalities. Methods： Animals can be divided into Male Tsumura Suzuki Diabetes（TSD） mice, Tsumura Suzuki normal（TSN） mice. Food intake in mice was monitored and blood chemistry was analyzed. Quantitative real-time polymerase chain reaction（PCR） assay was used to measure the expression level of feeding-related neuropeptide m RNA; radiation immunoassay was used to detect the protein level of nesfatin-1. Results： TSD mice showed an increase in body weight（P〈0.05） and hyperleptinemia（P〈0.05） from 1 month of age and hyperphagic feeding（P〈0.05）,hyperglycemia（P〈0.05）, hyperlipidemia（P〈0.05） and hyperinsulinemia（P〈0.05） from 3 to 12 months of age compared with age-matched non-diabetic control TSN mice. The m RNA and protein levels of nucleobindin-2（NUCB2）, the precursor of the anorexigenic neuropeptide nesfatin-1, was significantly decreased（P〈0.05~0.01） in the hypothalamus of TSD mice compared with that in TSN mice from 3 to 12 months of age. The m RNA levels of galanin, melanin-concentrating hormone, neuropeptide Y, and pro-opiomelanocortin were significantly changed（P〈0.05） in the hypothalamus in TSD mice at several time points. Conclusions： The results suggest that the disrupted control of hypothalamic NUCB2-mediated signaling may contribute to hyperphagic feeding in TSD mice.
出处
《现代生物医学进展》
CAS
2015年第8期1440-1443,共4页
Progress in Modern Biomedicine
基金
国家自然科学基金项目(31071014
81100260
81270460
81300281
81470815)
青岛市科技局项目(13-1-4-170-jch
11-2-3-3-(2)-nsh
14-2-3-3-nsh)
