瘦素基因敲除肥胖大鼠的血糖及病理长期观察  

Long-time observation of blood glucose and pathological phenotype of leptin knockout obese rats

作　　者：张丽[1] 关菲菲[1] 张旭[1] 陈炜[1] 孙彩显 张连峰[1] 

机构地区：[1]中国医学科学院,北京协和医学院,医学实验动物研究所,卫生部人类疾病比较医学重点实验室,北京100021

出　　处：《中国比较医学杂志》2014年第3期45-49,I0007,共6页Chinese Journal of Comparative Medicine

基　　金：国家"重大新药创制"科技重大专项课题"啮齿类研发平台创新药物研究开发技术平台建设"(2011ZX09307-302);国家科技支撑计划课题"神经和代谢疾病基因工程模型的建立"(2012BAI39B02)

摘　　要：目的：对Leptin基因敲除SD大鼠血糖变化及病理表型进行长期分析，为使用该大鼠作为糖尿病和脂代谢模型积累数据。方法 western blot检测Leptin＋/＋大鼠和Leptin-/-大鼠肝脏中Leptin的表达。利用称量方法测定Leptin基因敲除的SD大鼠（Leptin-/-）1，3，6，8月龄的体重变化，利用稳豪血糖仪采尾血测定1，3，6，8月龄Leptin-/-大鼠空腹血糖值。 HE染色和免疫组织化学观察Leptin-/-大鼠胰腺及肝脏的病理学变化。结果 Leptin-/-大鼠肝脏中表达变短的功能异常的Leptin蛋白。 Leptin-/-大鼠从1月龄开始出现显著的体重增加，8月龄时雌性体重为884 g，雄性体重可以达到1200 g，是野生SD大鼠的2倍。自1月龄起， Leptin-/-雌鼠的空腹血糖值显著高于野生大鼠，在1月龄到6月龄之间差别明显（40％～26％），到8月龄和野生大鼠恢复到近正常水平。8月龄Leptin-/-大鼠肝脏肝小叶中出现大量脂肪空泡，胰腺内较多脂肪细胞浸润、胰岛数量明显增多，体积增大，胰岛素阳性β细胞增多。结论 Leptin-/-大鼠表型表现为肥胖，脂肪肝，胰岛增生和早期高血糖。Objective To obtain more physiological data of Leptin knockout SD rats available for the user , the long-term observation of fasting blood glucose and pathological phenotypes were performed .Methods The protein expression levels in liver tissues were determined by western blot .Body weight of Leptin knockout rats （ Leptin-/-） and littermate lean rats （Leptin＋/＋） were weighed up at 1,3,6,8 months of age.Fasting blood glucose of Leptin ＋/＋rats and Leptin-/-rats at 1,3,6,8 months of age were measured using One Touch？ brand blood glucose monitoring systems.Pathological changes of pancreas and livers of Leptin -/-rats were observed by the method of HE staining and Immunohistochemistry （IHC）.Results Short null Lepin proteins were expressed in liver tissues from Leptin -/-rats. Leptin-/-rats become heavier than Leptin ＋/＋rats since they were one month old .The body weight of Leptin -/-rats at 8 months of age was twice as heavy as Leptin ＋/＋rats, female Leptin-/-rats weighing 884g, and male Leptin-/-rats weighing 1200g.Overt hyperglycemia was observed during the first month after birth .Compared with Leptin＋/＋female rats,the fasting blood glucose of Leptin -/-female rats was increased by 40%-26%from 1 to 6 months old. After that, blood glucose values decreased and eventually become nearly normal at 8 months of age.Pathological examination indicated that Leptin -/-rats at 8 months of age had a fatty liver , more pancreas islets with lager volume and more beta cells with increased insulin secretion .Conclusion Leptin-/-rat were characterized by obesity , fatty liver, islet cell hyperplasia and early hyperglycemia .

关 键 词：瘦素 基因敲除 空腹血糖 肥胖 大鼠 

分 类 号：R332[医药卫生—人体生理学]