热量限制对 C57小鼠学习记忆能力及胰岛素信号通路相关蛋白的影响

Effects of caloric restriction on learning and memory function and insulin signaling related protein in C57 mice

目的探讨热量限制(caloric restriction,CR)对C57小鼠学习、记忆能力及胰岛素信号通路相关蛋白的影响。方法雄性C57小鼠30只,采用数字表法随机分为3组:正常对照组(n=10)、高能量组(n=10)、低能量组(n=10)。6个月后通过Morris水迷宫检测各组小鼠的学习、记忆能力,每组各抽取5只应用免疫组织化学染色的方法,测定小鼠脑内胰岛素信号转导通路相关蛋白:依赖于烟酰胺腺嘌呤二核苷酸的组蛋白脱乙酰酶(silent mating type information regulation 2 homolog-1,SIRT1)、胰岛素样生长因子-1(insulin-like growth factor 1,IGF-1)、胰岛素受体(insulin receptor,IR)、胰岛素受体底物-1(insulin receptor substrate-1,IRS-1)、磷脂肌醇3激酶(phosphatidylinositol 3-kinase,PI3K)、蛋白激酶B(protein kinase B,Akt/PKB)、磷酸化应答原件结合蛋白(c AMP-response element binding protein,p-CREB)的表达。结果低能组小鼠的逃避潜伏期缩短,表明学习和记忆能力较前增高,SIRT1、IGF-1、IR、IRS-1、PI3K、Akt/PKB、p-CREB表达均明显降低(P<0.01)。结论热量饮食提高C57小鼠的学习记忆能力,可能与降低小鼠脑内胰岛素信号通路相关蛋白的表达有关。

Objective To investigate the effect of caloric restrictionon（CR） on learning and memory function and insulin signaling related protein in C57 mice. Methods Thirty male C57 mice were randomly divided into 3 groups： normal control group, high-energy group and low energy group, each group consisted of 10 mice, learning and memory function were measured by Morris test at the sixth month. Five mouse of each group were selected to measurethe insulin signaling pathway related protein by immunochemistry. Results The escape latency of low-energy group was shorter than normal control group, which indicates the learning and memory ability of low-energy C57 mice improved. The expression of Silent mating type information regulation 2 homolog- 1（SIRT1）, insulin-like growth factor 1 （IGF-1）, insulin receptor（IR）, insulin receptor substrate-1 （ IRS-1）, phosphatidylinositol 3-kinase（ PI3K）, protein kinase B（ Akt/PKB）, cAMP-response element binding protein（p-CREB）in brain decreased significantly as compared with normal control group（P〈0. 01）. Conclusion Caloric restriction can improve the learning and memory ability in C57 mice, probably through downregulate the expression of insulin signaling pathway related protein in brain.