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

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。

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 todetect 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（P0.05） and the total cholesterol（P0.01） from newborn IUGR rats were decreased.In weaning rats,triglyceride increased in the IA and IH groups compared to all the control groups（P0.05）;total cholesterol was lower in CR group compared with CA group（P0.05）,while it was higher in CH,IA and IH groups than in CR group（P0.05）,and lower in IR group than in IA group（P0.05）.In adult rats,total cholesterol was higher in CH,IA and IH groups compared with the CA group（P0.05）.The body mass of weaning rats of CH group increased（P0.05） and that of CR,IA and IR groups decreased（P0.05）compared to the CA group;the brain mass in weaning rats decreased in CR,IA,IH and IR groups compared to the CA group（P0.05）;brain-to-body mass ratio in weaning rats increased in CR and IR groups（P0.05） and decreased in CH group（P0.05）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（P0.05）;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（P0.05）.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.