摘要：哺乳动物冬眠状态下有很多特点，表现为极低的代谢速率、较低的体温和缓慢的血 液流速。 哺乳动物的人工冬眠可以为临床上缺血再灌注的保护、癌症治疗以及低温损 害的保护等提供可能的治疗手段和研究的动物模型。本课题使用 5’-AMP 诱导小鼠进入人 工冬眠状态，采用基于核磁共振氢谱技术的代谢组分析技术，结合多维统计分析方法检 测冬眠状态中的小鼠以及从冬眠中恢复后的小鼠与正常小鼠内源性小分子代谢物的区 别，从代谢变化的角度分析 5’-AMP 诱导人工冬眠用于临床的安全性。分析结果发现，冬 眠状态下的小鼠能量代谢相关代谢物质与正常小鼠有很大差异，但在从冬眠中恢复后的 小鼠代谢与正常小鼠除少量代谢物有差别，整体基本无异。

关键词 人工冬眠 5’-AMP 代谢组学 代谢通路

Title Effects of artificial hibernation on the metabolism in mice

Abstract：Mammalian hibernation has many characteristics, including a very low metabolic rate, slightly low body temperature and slow blood flow. Artificial mammalian hibernation can provide possible treatment and animal models for cancer, clinical protection of ischemia-reperfusion, and protection of low-temperature damage. In this study, 5'-AMP-induced-artificial hibernation was used in mice. Metabolomics analysis technique based on nuclear magnetic resonance spectroscopy together with multivariate statistical analysis method were taken advantage, hence to detect the difference of endogenous small molecule metabolites among mice in the hibernation state, mice recovered from the hibernation and normal mice. On this basis, safety of using 5’-AMP induced artificial hibernation for clinical was analyzed from the perspective of metabolic changes. The results indicated that the metabolic substances related to energy metabolism of mice in hibernation were distinct from those of normal mice. However, there was few difference between the metabolic substances of mice after hibernation and those of normal mice.

Keywords   artificial hibernation  5’-AMP  metabolomics  metabolic pathway

目 次

1 引言… 1

1.1 人工冬眠… 1

1.2 代谢组学… 4

2 材料与方法… 7

2.2 实验方法 8

3 实验结果… 10

3.1 血清代谢变化 10

3.2 肝代谢变化… 11

3.3 肾代谢变化… 17

3.4 脑代谢变化… 23

4 讨论 29

4.1 各组织代谢差异 29

4.2 能量代谢通路 29

结论 31

致谢 32

参考文献…