【摘要】 目的 探讨生酮饮食（KD）能否通过调节阿尔茨海默病模型小鼠大脑代谢及神经炎症促进认知。材料与方法 将20只APP/PS1雄性小鼠随机分为KD组（APP/PS1+KD）与普通饮食组（APP/PS1），每组10只；同时以10只野生型C57BL/6雄性小鼠作为对照组。使用生酮饲料喂养APP/PS1+KD组，普通饲料喂养APP/PS1组和对照组，共4个月。连续喂养4周、4个月后，记录小鼠的血酮，并使用Morris水迷宫评估小鼠认知，再行¹⁸F-FDG和¹⁸F-DPA-714 micro PET/CT分别评估KD对阿尔茨海默病小鼠各脑区葡萄糖代谢及神经炎症的影响；完成PET/CT显像后取脑组织，选择海马CA1区制成石蜡切片进行免疫荧光检测胶质纤维酸性蛋白、离子化钙结合适配分子表达情况。结果 4个月时，与对照组相比，APP/PS1组第3～4天逃避潜伏期显著延长（P<0.01、P<0.05）。与对照组相比，APP/PS1组在纹状体、海马、背侧丘脑、中央灰质、上丘、嗅球、中脑等脑区对¹⁸FFDG的标准化摄取值比值显著下降（P<0.05或P<0.01）；与APP/PS1组相比，APP/PS1+KD组海马、背侧丘脑对¹⁸F-FDG的标准化摄取值比值显著升高（P<0.01）。与对照组相比，APP/PS1组纹状体、海马、下丘脑等脑区对¹⁸F-DPA-714的标准化摄取值比值显著上升（P<0.05或P<0.001）；与APP/PS1组相比，APP/PS1+KD组降低了海马区相对¹⁸F-DPA-714摄取（P<0.01）。与对照组、APP/PS1+KD组相比，APP/PS1组小鼠脑（海马）胶质纤维酸性蛋白、离子化钙结合适配分子表达显著升高（P均<0.01）。结论 KD可通过提高APP/PS1小鼠大脑代谢并抑制神经炎症，促进其认知行为学改善。更多还原

【Abstract】 Purpose To investigate whether ketogenic diet（KD） can promote cognition by regulating brain metabolism and neuroinflammation in Alzheimer′s disease model mice. Materials and Methods Twenty male APP/PS1 mice were randomly assigned to either a KD group（APP/PS1+KD） or a regular diet group（APP/PS1）, with 10 mice in each group. Additionally, 10 wild-type C57BL/6 male mice served as the control group. The APP/PS1+KD group was fed with a ketogenic feed, the APP/PS1 group received a regular diet, and the control group was maintained on standard chow for a duration of 4 months. Blood ketone levels of mice were monitored after 4 weeks and 4months of continuous feeding. Cognitive function was assessed via the morris water maze. ¹⁸F-FDG and ¹⁸F-DPA-714 micro PET/CT were performed to evaluate the effects of KD on glucose metabolism and neuroinflammation across various brain regions in the Alzheimer’s disease mice. Following PET/CT imaging, brain tissue samples were collected, and the hippocampal CA1 region was selected for paraffin sectioning to detect the expression of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 through immunofluorescence analysis.Results In the Morris water maze in the fourth month, compared with the control group, the APP/PS1 group had a significantly longer escape latency on days 3-4（P<0.05 or P<0.01）. Compared with the control group, the APP/PS1 group showed a significant decrease in relative ¹⁸F-FDG uptake in brain regions such as the striatum, hippocampus, dorsal thalamus, central gray matter, superior colliculus, olfactory bulb, and midbrain（P<0.01, P<0.05）. Compared with the APP/PS1 group, the APP/PS1+KD group showed a significant increase in relative ¹⁸F-FDG uptake in the hippocampus and dorsal thalamus（P<0.01）. Compared with the control group, the APP/PS1 group showed a significant increase in relative uptake of ¹⁸F-DPA-714 in brain regions such as the striatum, hippocampus and hypothalamus（P<0.05 or P<0.001）. Compared with the APP/PS1 group, the APP/PS1+KD group decreased the relative uptake of ¹⁸F-DPA-714 in the hippocampus（P<0.01）. Compared with the control group and APP/PS1+KD group, the fluorescence intensity of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 protein in the brain（hippocampus） of APP/PS1 group mice was significantly increased（both P<0.01）. Conclusion KD has the potential to ameliorate cognitive and behavioral deficits in APP/PS1 mice by enhancing brain metabolism and attenuating neuroinflammation.更多还原