出生后营养干预对宫内发育迟缓大鼠学习记忆的影响

doi:10.3969/j.issn.1006-7795.2017.06.015

首都医科大学学报 ›› 2017, Vol. 38 ›› Issue (6): 851-856.doi: 10.3969/j.issn.1006-7795.2017.06.015

• 神经系统疾病的基础和临床研究 • 上一篇下一篇

出生后营养干预对宫内发育迟缓大鼠学习记忆的影响

徐世明¹, 王宏娟¹, 李中秋¹, 古同男¹, 许子华¹, 盛树力²

1. 首都医科大学燕京医学院生化与分子生物学教研室, 北京 101300;
2. 首都医科大学宣武医院中心实验室, 北京 100053

收稿日期:2017-10-01 出版日期:2017-11-21 发布日期:2017-12-16
通讯作者: 王宏娟 E-mail:whj1006@163.com
基金资助:
北京市自然科学基金（7132033），首都医科大学基础－临床合作基金（16JL14），燕京医学院科研基金（15QD02，15QD08，17QD05）。

Effect of postnatal nutritional intervention on learning and memory of intrauterine growth retardation rats

Xu Shiming¹, Wang Hongjuan¹, Li Zhongqiu¹, Gu Tongnan¹, Xu Zihua¹, Sheng Shuli²

1. Department of Biochemistry and Molecular Biology, Yanjing Medical College, Capital Medical University, Beijing 101300, China;
2. Central Laboratory, Xuanwu Hospital, Capital Medical University, Beijing 100053, China

Received:2017-10-01 Online:2017-11-21 Published:2017-12-16
Supported by:
This study was supported by Natural Science Foundation of Beijing (7132033), Basic-clinical Cooperation Fund of Capital Medical University(16JL14), Yanjing Medical College Research Fund(15QD02,15QD08,17QD05).

摘要/Abstract

摘要： 目的研究营养干预对宫内发育迟缓（intrauterine growth retardation，IUGR）大鼠学习记忆的影响，探讨阿尔茨海默病（Alzheimer's disease，AD）等神经变性病可能的发育起源及营养相关机制。方法应用热量限制法制备IUGR大鼠模型。对出生后的对照大鼠（control，C）和IUGR大鼠（I）在哺乳期和断乳后分别给予自由取食标准饲料（ad libitum food intake，A）、限制取食70%标准饲料（restricted food intake，R）及自由取食高脂饲料（high fat food intake，H）处理，得到6组大鼠：对照自由取食（control with ad libitum food intake，CA）组、对照限制取食（control with restricted food intake，CR）组、对照自由取食高脂（control with high fat food intake，CH）组、IUGR自由取食（IUGR with ad libitum food intake，IA）组、IUGR限制取食（IUGR with restricted food intake，IR）组和IGRU自由取食高脂（IUGR with high fat food intake，IH）组。于新生、断乳和成年3个不同时期取材，比较各组大鼠体质量、脑质量、脑/体质量比、血糖、血三酰甘油和总胆固醇等指标的变化。应用Morris水迷宫实验，比较各组成年大鼠空间学习记忆能力的变化。结果新生IUGR大鼠的血糖和总胆固醇浓度与对照组相比降低，差异有统计学意义（P<0.05）。断乳期，血三酰甘油在IA和IH组较正常出生体质量组升高（P<0.05）；血总胆固醇在CR组低于CA组（P<0.05），CH、IA和IH组高于CR组（P<0.05），IR组低于IA组（P<0.05）。成年大鼠血总胆固醇浓度在CH、IA和IH组均高于CA组（P<0.05）。断乳大鼠体质量，CH组高于CA组（P<0.05），CR、IA和IR组均低于CA组（P<0.05）；脑质量，CR、IA、IH、IR组均低于CA组（P<0.05）；脑/体质量比在CR和IR组高于CA组（P<0.05），CH组低于CA组（P<0.05）。成年大鼠的脑、体质量变化与断乳时期相似。Morris水迷宫实验中，撤除平台后，CH及IR两组大鼠穿过平台的次数均多于CA组（P<0.05）；CH组大鼠在平台象限停留时间多于CA、CR和IR组，差异有统计学意义（P<0.05）。结论出生后的不同营养干预可造成IUGR大鼠血糖、血脂等血液生物化学指标的变化，伴脑、体质量的差异及成年后空间学习记忆的改变，提示AD等神经变性病的脑内变化可能起源于生命早期，并受到生后营养状况的影响。

关键词: 宫内发育迟缓, 营养干预, 脑/体质量比, Morris水迷宫

Abstract: Objective In order to explore the possible developmental origins and related mechanisms of nutrition in neurodegenerative disease like Alzheimer disease (AD), we observed the changes of learning and memory ability of rats with intrauterine growth retardation (IUGR) under different nutritional intervention.Methods IUGR rats were induced by calorie restriction on pregnant rats. After birth, control (C) rats and IUGR (I) rats were fed with ad libitum food intake (A), 70% restricted food intake (R) and high fat food intake (H) respectively, and 6 groups of rats with different nutritional intervention were obtained:control with ad libitum food intake (CA), control with restricted food intake (CR), control with high fat food intake(CH), IUGR with ad libitum food intake (IA), IUGR with restricted food intake (IR) and IUGR with high fat food intake (IH). Body mass, brain mass, brain:body mass ratio, blood sugar, triglyceride and total cholesterol were determined at the period of newborn, weaning and adult. Morris water maze (MWM) was used to detect the changes of learning and memory ability in adult rats. SPSS 18.0 was applied to analyze the data. Results Compared with the control group, the blood sugar (P<0.05) and the total cholesterol (P<0.01) from newborn IUGR rats were decreased. In weaning rats, triglyceride increased in the IA and IH groups compared to all the control groups (P<0.05); total cholesterol was lower in CR group compared with CA group (P<0.05), while it was higher in CH, IA and IH groups than in CR group (P<0.05), and lower in IR group than in IA group (P<0.05). In adult rats, total cholesterol was higher in CH, IA and IH groups compared with the CA group (P<0.05). The body mass of weaning rats of CH group increased(P<0.05)and that of CR, IA and IR groups decreased(P<0.05)compared to the CA group; the brain mass in weaning rats decreased in CR, IA, IH and IR groups compared to the CA group(P<0.05); brain-to-body mass ratio in weaning rats increased in CR and IR groups(P<0.05)and decreased in CH group(P<0.05)compared to CA group. The varieties of body and brain mass in adult rats were similar to that in weaning rats. In Morris water maze test, when the platform was removed, it was detected that rats of CH and IR groups crossed the platform more frequently than the ones from CA group(P<0.05); the rats of CH group stayed in the quadrant where the platform was placed before for a longer time than the rats of CA, CR and IR group(P<0.05).Conclusion Nutritional interventions on IUGR rats resulted in the changes of blood sugar, triglyceride and total cholesterol, which thus affected the body and brain mass, which might be involved in the variety of ability of learning and memory in adult rats. It indicated that the changes in the brain of neurodegenerative disease like AD might derived from early life and be affected by the nutritional circumstance after birth.

Key words: intrauterine growth retardation, nutritional intervention, brain-body mass ratio, Morris water maze

中图分类号:

R722

徐世明, 王宏娟, 李中秋, 古同男, 许子华, 盛树力. 出生后营养干预对宫内发育迟缓大鼠学习记忆的影响[J]. 首都医科大学学报, 2017, 38(6): 851-856.

Xu Shiming, Wang Hongjuan, Li Zhongqiu, Gu Tongnan, Xu Zihua, Sheng Shuli. Effect of postnatal nutritional intervention on learning and memory of intrauterine growth retardation rats[J]. Journal of Capital Medical University, 2017, 38(6): 851-856.

参考文献

[1] Powell K L, Stevens V, Upton D H, et al. Role for the thromboxane A2 receptor beta-isoform in the pathogenesis of intrauterine growth restriction[J]. Sci Rep,2016, 6(1):28811.
[2] Thorn S R, Rozance P J, Brown L D, et al. The intrauterine growth restriction phenotype:fetal adaptations and potential implications for later life insulin resistance and diabetes[J]. Semin Reprod Med,2011, 29(3):225-236.
[3] Polat A, Barlow S, Ber R, et al. Volumetric MRI study of the intrauterine growth restriction fetal brain[J]. Eur Radiol,2017, 27(5):2110-2118.
[4] 王宏娟,徐世明,李中秋,等. 新生IUGR大鼠脑内胰岛素信号通路相关蛋白表达的变化[J]. 基础医学与临床,2013,33(10):1061-1065.
[5] 陈璐,刘翠萍,袁庆新,等. 宫内发育迟缓对新生大鼠胰腺发育及功能的影响[J]. 南京医科大学学报:自然科学版,2008, 28(3):278-281.
[6] Duarte A I, Candeias E, Correia S C, et al. Crosstalk between diabetes and brain:glucagon-like peptide-1 mimetics as a promising therapy against neurodegeneration[J]. Biochim Biophys Acta,2013, 1832(4):527-541.
[7] Hoyer S. Is sporadic Alzheimer disease the brain type of non-insulin dependent diabetes mellitus? A challenging hypothesis[J]. J Neural Transm,1998, 105(4-5):415-422.
[8] Benoit J D, Rakic P, Frick K M. Prenatal stress induces spatial memory deficits and epigenetic changes in the hippocampus indicative of heterochromatin formation and reduced gene expression[J]. Behav Brain Res,2015, 281(1):1-8.
[9] Goodspeed D, Seferovic M D, Holland W, et al. Essential nutrient supplementation prevents heritable metabolic disease in multigenerational intrauterine growth-restricted rats[J]. FASEB J, 2015, 29(3):807-819.
[10] Dong W, Wang R, Ma L N, et al. Influence of age-related learning and memory capacity of mice:different effects of a high and low caloric diet[J]. Aging Clin Exp Res,2016, 28(2):303-311.
[11] Kim H E, Grant A R, Simic M S, et al. Lipid biosynthesis coordinates a mitochondrial-to-cytosolic stress response[J]. Cell,2016, 166(6):1539-1552.
[12] Dehghan M, Mente A, Zhang X, et al. Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE):a prospective cohort study[J]. Lancet,2017, 390(10107):2050-2062.
[13] 王升武. 阿尔茨海默病的临床特征及综合治疗效果的评价[J]. 医学理论与实践, 2016, 29(3):319-321.
[14] Macko A R, Yates D T, Chen X, et al. Adrenal demedullation and oxygen supplementation independently increase glucose-stimulated insulin concentrations in fetal sheep with intrauterine growth restriction[J]. Endocrinology, 2016, 157(5):2104-2115.
[15] 王玉惠. 早产儿不同肠外营养方案的临床探讨[J]. 吉林医学, 2014, 35(25):5624-5626.

出生后营养干预对宫内发育迟缓大鼠学习记忆的影响

Effect of postnatal nutritional intervention on learning and memory of intrauterine growth retardation rats

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 1

编辑推荐

Metrics

本文评价