【Animal modeling】-Mechanism of jujube saponins alleviating Alzheimer

  Objective To investigate the mechanism of jujube saponin (ZSS) alleviating sevoflurane anesthesia in 9-month-old APP/PS1/tau triple transgenic Alzheimer's disease model mice.

  Methods Nine-month-old male APPSwe/ PS1M146 V/tauP301 L 3xTg-AD 3xTg-AD mice and their background C57BL/6J mice were selected and divided into four groups according to the principle of random assignment, with 12 mice in each group, namely: 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), three-turn model administration group Group 2 (normal saline + sevoflurane) +ZSS). All mice were injected with equal volume of normal saline or 0.1μg/4μL of jujube saponins through the lateral ventricle for 10 days. The mice in the control group were inhaled with oxygen for 2 hours, and the mice in the anesthesia group and the administration group were inhaled with sevoflurane for 2 hours. 24h after anesthesia, 6 mice in each group were used to test the spatial learning and memory ability of the mice by Morris water maze. From other mice, fresh hippocampal tissue was taken by decapitation and prepared into a homogenate, and the aggregation of amyloid beta (Aβ) (Aβ, Aβ1-40, Aβ1-42) was detected by Western blot. The phosphorylation of Tau protein and the phosphorylation levels of its sites (serine 396, serine 262, threonine 231) were detected, and the mitochondrial apoptosis signaling pathway genes, including B lymphoma cells, were detected by Real-time PCR technology. Changes in the expression of -2 gene (BcL-2), BcL-2-related X protein (Bax) and caspase (Caspase-3).

  Results The Morris water maze test showed that sevoflurane had no effect on the learning and memory ability of mice, but had potential neurotoxicity in mice; jujube saponins could reduce Aβ aggregation and Tau protein phosphorylation in three-transformation model mice; Compared with the three-turn model anesthesia group, the expression of BcL-2 in the three-turn model administration group was decreased, while the expressions of Bax and Caspase-3 were enhanced.

  CONCLUSIONS: Jujube saponin can alleviate the activation of mitochondria-related apoptosis signaling pathway by sevoflurane anesthesia, reduce Aβ aggregation, reduce Tau protein phosphorylation, and inhibit the apoptosis of mouse hippocampal neurons.