[Animal modeling] - Study on the mechanism of jujuboside in alleviating Alzheimer's disease model mice

  Objective To investigate the mechanism of jujuboside (ZSS) in alleviating sevoflurane anesthesia in 9-month-old APP/PS1/tau transgenic mice with Alzheimer disease.

  Methods Nine month old male APPSwe/PS1M146 V/tauP301 L 3xTg AD 3xTg AD mice and their background C57BL/6J mice were selected and randomly divided into four groups with 12 mice in each group: wild control group Con (normal saline), three turn model control group Model Con (normal saline), three turn model anesthesia group Group 1 (normal saline+sevoflurane) and three turn model administration group 2 (normal saline+sevoflurane+ZSS). All mice were injected with normovolemic saline or 0.1 through the lateral ventricle μ g/4 μ L of Ziziphus spinosaponins for 10 days. The control group mice inhaled 2h oxygen, and the anesthesia group and the administration group inhaled 2h sevoflurane. Twenty four hours after anesthesia, six mice in each group were used Morris water maze to test their spatial learning and memory abilities. Other mice took fresh hippocampal tissue by decapitation, prepared it into homogenate, and detected b amyloid peptide (A) by Western blot β) Aggregation (A β、 A β 1-40、A β 1-42). At the same time, we also detected the phosphorylation of Tau protein and the change of phosphorylation level of its sites (serine 396, serine 262, threonine 231), and detected the change of mitochondrial apoptosis signal pathway genes, including the expression of B lymphoblastoma 2 gene (BcL-2), BcL-2 related X protein (Bax), and caspase-3.

  Results Morris water maze test showed that sevoflurane had no effect on the learning and memory ability of mice, but had potential neurotoxicity to mice; Ziziphus spinosaponins can reduce the content of A in mice β Aggregation and tau protein phosphorylation; Compared with the three turn model anesthesia group, the expression of BcL-2 in the three turn model administration group decreased, and the expression of Bax and Caspase-3 increased.

  Conclusion Ziziphus jujuboside can alleviate the apoptosis signal pathway related to sevoflurane anesthesia activated mitochondria, and reduce A β Gather, reduce tau protein phosphorylation, and inhibit apoptosis of hippocampal neurons in mice.