目的 观察APP/PS1转基因鼠海马区中代谢物的变化与超微病理改变之间的联系,使该基因鼠更好地应用于阿尔茨海默病(AD)的实验研究.方法 通过新物体识别实验比较APP/PS1转基因鼠和同龄、同背景野生鼠的学习记忆能力;通过氢质子磁共振波谱(1HMRS)检测比较两组海马区N-乙酰天冬氨酸(NAA)、肌醇(mI)、胆碱(Cho)和谷氨酸(Glu)等代谢物的含量;通过透射电镜观察神经细胞和星形胶质细胞的超微结构.结果与野生鼠相比,转基因鼠学习记忆能力下降,两组间差异有统计学意义(P<0.05);海马区NAA与肌酸(Cr)比值明显减少(P<0.05),mI/Cr和Cho/Cr增加(P<0.05);神经细胞和星形胶质细胞线粒体变性、固缩,次级溶酶体数量增加,星形胶质细胞过度活化、吞噬营养障碍性突触.结论 APP/PS1 转基因小鼠海马区 NAA、mI、Cho 等代谢物的变化可以反映AD病变过程中β-淀粉样蛋白诱发的异常炎症反应和突触结构的破坏等病理特征,为APP/PS1基因鼠更好地应用于AD研究提供实验依据.
Objective: This study aimed to explore the neuroprotective effect of Baihe Dihuang Tang (BDT), a traditional Chinese herbal decoction used for nervous-mental system diseases, on serum-deprived PC12 cell. Methods: BDT treatment time and concentration were determined through 4,5-dimethylthiazol-2-y1,2,5-diphenyl tetrazolium (MU) assay. PC12 cells were randomly divided into three groups: control (cells cultured in serum-containing medium), model (cells cultured in serum-deprived medium), and BDT (cells cultured in serum-deprived medium and treated with 3 mg/mL BDT for 24 h) groups. Cell morphology was observed under an inverted phase contrast microscope. The ultrastructure of cells was studied under a transmission electron microscopy. Membrane potential was determined using a laser scanning confocal microscope. Total protein and ATP levels were analyzed by the bicinchoninic acid method and firefly luciferase method, respectively. Results: Compared with the model group, PC12 cells in the BDT group exhibited extensive morphology and adhered to the culture plate. The ultrastructure was modified and possessed a smooth membrane and nuclear surface, increased microvilli-like membrane protrusions, homogeneously distributed organelles, rare pinocytosis and phagocytosis, abundant ribosomes, rare vacuoles, and normal-shaped nucleus. BDT also enhanced the total cell protein content, ATP level, and membrane hyperpolarization. Conclusion: BDT could reduce cell death and neural excitability and regulate energy metabolism caused by serum deprivation. We suggest that BDT could modify the hypometabolic state and neural overactivity in chronic fatigue syndrome (CFS). This work may provide new insights into the possibility of using BDT as a therapeutic agent for CFS.
Alzheimer’s disease (AD) is one of the main pathogenies of the cognitive decline in aging population. Paeoniflorin is a water-soluble monoterpene isolated from the roots of Paeonia lactiflora or P. suffruticosa, which are both in the family Ranunculaceae. Paeoniflorin has the effect of improving the cognitive ability, sedative, anti-inflammatory, analgesic, and spasmolytisch activities. It could also regulate hyperphosphorylation of Tau and Aβ proteins; Paeoniflorin can restore the balance of neurotransmitter and neurotransmitter receptors including acetylcholine, nerve growth factor, calcium ion, α7 nicotinic acetylcholine receptor and adenosine receptors, and reduce inflammation, oxidative stress and neuron apoptosis in AD animal and cell models. This paper reviewed relevant research in the past decade about the effect of paeoniflorin on AD, which may provide theoretical basis to use agent from Chinese medicine for AD prevention and treatment.
