地黄饮子通过NDRG2 调节突触可塑性改善APP/PSI双转基因小鼠认知功能的作用OA
Effects of Dihuang Yinzi on Improving the Cognitive Function of APP/PSI Double Transgenic Mice by Regulating Synaptic Plasticity via NDRG2
目的:研究地黄饮子对APP/PS1 双转基因小鼠认知功能的影响,并探寻其作用机制.方法:将45 只雄性APP/PS1 双转基因小鼠随机分为 5 组,每组9 只,即模型组(给予生理盐水)、盐酸多奈哌齐组(给予盐酸多奈哌齐0.84 mg·kg-1·d-1)、地黄饮子低、中、高剂量组(分别给予地黄饮子 1.25、2.5、5 g·kg-1·d-1);并将9 只雄性C57BL/6J小鼠作为空白组(给予生理盐水),连续干预 4 周.4 周后,采用Morris水迷宫实验评估各组小鼠空间学习记忆能力;尼氏染色观察海马CA3 区神经元细胞及尼氏小体;免疫组化(IHC)染色观察海马组织CA3 区NDRG2、GFAP;高尔基染色观察海马组织CA3 区锥体神经元棘突形态;免疫荧光染色检测海马组织CA3 区突触后致密物-95(PSD95)、突触素SYN表达;Western blot检测海马NDRG2、EAAT1 表达水平.结果:与模型组比较,地黄饮子各剂量组Morris水迷宫逃避潜伏期减少(P<0.05,P<0.01),目标象限停留时间及目标象限穿越次数均增加(P<0.05,P<0.01),神经元数量、树突分支数及树突棘有所增加,PSD95、SYN 上调(P<0.05,P<0.01),GFAP、NDGR2、EAAT1 有所减少(P<0.05,P<0.01).结论:地黄饮子可改善APP/PS1 双转基因小鼠的认知功能,其作用机制可能与下调NDRG2 的表达,调控星形胶质细胞,继而下调EAAT1,降低突触间隙谷氨酸浓度,改善突触可塑性,减轻海马神经元损伤有关.
Objective:To investigate the effects of Dihuang Yinzi on cognitive function of APP/PS1 double transgenic mice and explore its underlying mechanisms.Methods:Forty-five male APP/PS1 double transgenic mice were randomly divided into 5 groups(9 mice per group):namely the model group(normal saline),the donepezil hydrochloride group(0.84 mg/kg/d),and the low-dose,medium-dose,and high-dose Dihuang Yinzi groups(1.25,2.5,and 5 g/kg/d,respectively).Additionally,9 male C57BL/6J mice were used as the blank group(normal saline).All groups were treated continuously for 4 weeks.After 4 weeks,the Morris water maze test was used to evaluate spatial learning and memory abilities in each group.Nissl staining was performed to observe neuronal cells and Nissl bodies in the CA3 region of the hippocampus.Immunohistochemical(IHC)staining was used to observe NDRG2 and GFAP in the CA3 region of the hippocampus.Golgi staining was used to examine the morphology of dendritic spines in pyramidal neurons in the CA3 region of the hippocampus.Immunofluorescence staining was used to detect the expression of postsynaptic density protein-95(PSD95)and synaptophysin(SYN)in the CA3 region of the hippocampus.Western blot was used to measure the expression of NDRG2 and EAAT1 in the hippocampus.Results:Compared with the model group,the escape latency of the Morris water maze in each dose group of Dihuang Yinzi was reduced,and the residence time in the target quadrant and the number of crossings in the target quadrant were increased(P<0.01 or P<0.05).The number of neurons,the number of dendritic branches,and dendritic spines were increased.PSD95 and SYN were up-regulated(P<0.05),while GFAP,NDGR2,and EAAT1 were decreased(P<0.01 or P<0.05).Conclusion:Dihuang Yinzi can improve the cognitive function of APP/PS1 double transgenic mice.Its mechanism of action may be related to down-regulating the expression of NDRG2,regulating astrocytes,subsequently down-regulating EAAT1,reducing the concentration of glutamate in the synaptic cleft,improving synaptic plasticity,and alleviating hippocampal neuronal damage.
玛娜璐璐;梁丽丽;张庆;袁晓霞
新疆医科大学,新疆 乌鲁木齐 830017新疆医科大学,新疆 乌鲁木齐 830017乌鲁木齐市中医医院,新疆 乌鲁木齐 830002新疆医科大学,新疆 乌鲁木齐 830017
医药卫生
地黄饮子星形胶质细胞N-myc下游调节基因2突触可塑性
Dihuang YinziAstrocytesN-myc downstream regulatory gene 2Synaptic plasticity
《中医药学报》 2026 (3)
15-23,9
新疆维吾尔自治区自然科学基金项目(2021D01C2662020D01C174)
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