追赶生长饮食诱导小鼠代谢综合征并发脑衰老样病变模型的建立  

Establishment of a model for catch-up growth diet induced metabolic syndrome with brain aging symptoms in mice

作　　者：金贺[1] 赵志炜[1] 王玉兰[1] 张旭[1] 王蓉[1,2] JIN He;ZHAO Zhiwei;WANG Yulan;ZHANG Xu;WANG Rong(Central Laboratory, Xuanwu Hospital, Capital Medical University, Beijing Geriatric Medical ResearchCenter, Key Laboratory for Neurodegenerative Disease, Ministry of Education, Beijing 100053, China;Beijing Institute for Brain Disorders, Beijing 100053)

机构地区：[1]首都医科大学宣武医院中心实验室,北京市老年病医疗研究中心,神经变性病教育部重点实验室,北京100053 [2]北京脑重大疾病研究院,北京100053

出　　处：《中国实验动物学报》2018年第6期681-687,共7页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金(81600927);国家重点研发计划(2018YFA0108503).

摘　　要：目的通过追赶生长饮食诱导C57小鼠出现代谢综合征并发脑衰老样病变动物模型,并研究其可能的机制。方法 40只C57小鼠随机分为4组,正常对照组10只,低能量饮食组10只,高能量饮食组10只,追赶生长组(先低能饮食喂养6周再开放高能量饮食)10只,各组动物均连续喂养12周,记录体重、血糖,于实验末检测代谢综合征相关生化指标,计算胰岛素抵抗指数,Western blot技术检测衰老相关蛋白P53和磷酸化P53(ser15)表达水平,电镜下观察海马区脂褐素沉积情况。结果低能量组小鼠体重、血糖、代谢综合征相关生化指标(血清胆固醇、三酰甘油、胰岛素样生长因子1、胰岛素)以及P53和磷酸化P53蛋白表达水平低于正常对照组,脂褐素沉着较少;高能量组和追赶生长组代谢综合征指标显著高于对照组,并出现明显P53和磷酸化P53蛋白表达量增多以及脂褐素沉积;其中追赶生长组表现出更为明显的胰岛素抵抗倾向和脑衰老样变。结论追赶生长饮食喂养可诱导小鼠代谢综合征模型并发脑衰老样病变,本研究为饮食方式改变引起的代谢综合征及其并发症神经变性样变动物模型的构建提供研究新思路。Objective To investigate the mechanism underlying catch-up growth diet-induced metabolic syndrome and brain aging symptoms in C57mice.MethodsForty C57mice were randomly divided into four groups;a normal control group(n=10),a calorie-restricted group(n=10),a high-energy-diet group(n=10)and a catch-up growth group(calorie-restricted/high-energy-diet group,n=10).These animals were continuously fed for12weeks.The body weight and blood glucose of the animals were recorded,biochemical indicators of metabolic syndrome were detected at the end of the experiment,HOMA-IR was calculated,the expression levels of senescence-associated protein P53and phosphorylated P53(ser15)were determined by Western blot,and the lipofuscin deposited in the hippocampus was observed by electron microscopy.ResultsCompared with the normal control group,the calorie-restricted group had lower body weight,blood glucose,and biochemical indicators,its levels of P53and phosphorylated P53protein expression were downregulated,and lipofuscin deposition was reduced.Meanwhile,compared with the normal control group,the metabolic syndrome indicators of the high-energy group and the catch-up growth group were significantly higher,the levels of P53and phosphorylated P53protein expression were increased,and more lipofuscin deposition was observed.Furthermore,the catch-up growth group showed more pronounced insulin resistance and brain aging symptoms.ConclusionsA catch-up growth diet can induce metabolic syndrome in mice with brain aging.This study provides new research ideas for the construction of animal models with metabolic syndrome and neurodegenerative dysfunction caused by different dietary patterns.

关 键 词：追赶生长 代谢综合征 脑衰老 

分 类 号：Q95-33[生物学—动物学]