长期高脂饮食对视皮质和海马神经元突触可塑性影响的实验研究  

Long-term high-fat diet′s impact on synaptic plasticity in the visual cortex and hippocampus neurons:an experimental study

作　　者：吉晓静 郭雅图 张伟[2] Ji Xiaojing;Guo Yatu;Zhang Wei(Clinical College of Ophthalmology of Tianjin Medical University,Tianjin 300020,China;Tianjin Eye Hospital,Nankai University Affiliated Eye Hospital,Clinical College of Ophthalmology of Tianjin Medical University,Tianjin Eye Institute,Tianjin Key Laboratory of Ophthalmology and Visual Science,Tianjin 300020,China)

机构地区：[1]天津医科大学眼科临床学院,天津300020 [2]天津市眼科医院、南开大学附属眼科医院、天津医科大学眼科临床学院、天津市眼科研究所、天津市眼科学与视觉科学重点实验室,天津300020

出　　处：《中华眼科杂志》2023年第9期730-739,共10页Chinese Journal of Ophthalmology

基　　金：天津市科委重点研发计划科技支撑重点项目(19YFZCSY00990);天津市自然科学基金面上项目(18JCYBJC26500);天津市眼科医院重点项目(YKZD2004);天津市医学重点学科(专科)建设项目资助(TJYXZDXK-016A)。

摘　　要：目的探讨长期高脂饮食对幼年小鼠视皮质和海马神经元突触可塑性的影响及其机制。方法实验研究。24只4周龄雄性C57BL/6J小鼠按随机数字表法分为两组,每组12只。正常饮食(ND)组采用正常饮食喂养,高脂饮食(HFD)组采用高脂饮食喂养。喂养12周,记录小鼠体重和体脂比,进行葡萄糖耐量试验和血脂水平测定。采用随机数字表法每组选择6只小鼠,对丘脑视皮质外侧膝状体(LGN)-初级视皮质双眼区(V1B区)和海马CA3-CA1的长时程增强作用进行在体记录,测量场兴奋性突触后电位(fEPSP)并计算标准化的fEPSP斜率,以评估小鼠皮质突触可塑性变化,之后取脑组织进行高尔基染色,观察初级视皮质双眼区Ⅱ-Ⅲ层和海马CA1区锥体神经元胞体、轴突、树突发育情况,比较树突棘形态与数量的变化。处死每组其余6只小鼠,取脑组织,采用透射电镜观察视皮质V1B区和海马CA1区神经元超微结构变化。采用独立样本t检验进行统计学分析。结果喂养12周后,HFD组小鼠体重为(29.17±1.63)g,HFD组体重为(37.99±6.87)g,差异有统计学意义(t=4.33,P<0.001)。ND组体脂比为0.85%±0.09%,HFD组体脂比为1.09%±0.22%,差异有统计学意义(t=2.50,P=0.032)。HFD组小鼠在注射葡萄糖后30 min血糖水平升高显著,为(17.80±3.94)mmol/L,高于ND组的(23.10±1.48)mmol/L(t=3.07,P=0.013)。HFD组血糖水平下降缓慢,在注射葡萄糖后60 min,ND组与HFD组血糖水平差异最大,分别为(13.58±2.39)mmol/L和(23.70±3.56)mmol/L,差异有统计学意义(t=5.40,P<0.001)。之后两组血糖水平均开始下降,在注射葡萄糖后120 min,ND组血糖水平降至(8.50±1.05)mmol/L,而HFD组仍处于较高水平,为(16.03±4.17)mmol/L,差异有统计学意义(t=3.91,P=0.004)。ND组与HFD组小鼠血清总胆固醇水平分别为(4.08±0.35)和(10.80±0.90)mmol/L,HFD组高于ND组(t=15.23,P<0.001);甘油三酯水平差异无统计学意义(P>0.05)。ND组高密度脂蛋白胆固醇水平为(2.1Objective To investigate the effects and mechanisms of long-term high-fat diet on synaptic plasticity in the visual cortex and hippocampus neurons of juvenile mice.Methods This was an experimental study.Twenty-four 4-week-old male C57BL/6J mice were randomly divided into two groups,using a randomized numerical table,with 12 mice in each group.The ND group was fed a normal diet,while the HFD group was fed a high-fat diet.After 12 weeks of feeding,mouse body weight,body fat percentage,glucose tolerance,and blood lipid levels were recorded.Six mice from each group were randomly selected using a randomized numerical table,and long-term potentiation(LTP)in the lateral geniculate nucleus(LGN)-primary visual cortex binocular zone(V1B area)and hippocampus CA3-CA1 were recorded in vitro.Field excitatory postsynaptic potentials(fEPSPs)were measured,and the normalized fEPSP slope was calculated to evaluate changes in cortical synaptic plasticity.Subsequently,brain tissue was collected for Golgi staining to observe the development of pyramidal neurons in layersⅡ-Ⅲof the primary visual cortex and CA1 region of the hippocampus,and changes in dendritic spine morphology and quantity were compared.The remaining six mice from each group were euthanized,and brain tissue was collected for transmission electron microscopy to observe ultrastructural changes in the visual cortex V1B area and hippocampus CA1 region neurons.Independent samples t-test was used for statistical analysis.Results After 12 weeks of feeding,the body weight of mice in the HFD group was(29.17±1.63)g,significantly lower than the ND group which was(37.99±6.87)g(t=4.33,P<0.001).The body fat percentage in the HFD group was 1.09%±0.22%,which was higher than the ND group with 0.85%±0.09%(t=2.50,P=0.032).HFD mice showed a significant increase in blood glucose level 30 minutes after glucose injection,reaching(17.80±3.94)mmol/L,compared to the ND group with(23.10±1.48)mmol/L(t=3.07,P=0.013).At 60 minutes after glucose injection,the difference in blood glucose le

关 键 词：膳食 高脂 初级视皮质 海马 突触 神经元可塑性 小鼠 

分 类 号：R338[医药卫生—人体生理学]