Objective To investigate the mechanism of Jujube saponins (ZSS) alleviating sevoflurane anesthesia in 9-month-old APP/PS1/tau three-transgenic Alzheimer's disease model mice.
Methods 9-month-old male APPSwe/PS1M146 V/tauP301 L 3xTg-AD 3xTg-AD mice and their background C57BL/6J mice were selected. According to the principle of random allocation, they were divided into four groups, each with 12 mice, respectively: 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 isometric normal saline or 0.1μg/4μL jujuboside via lateral ventricle for 10 consecutive days. The control group mice inhaled oxygen for 2h, the anesthesia group and the administration group inhaled sevoflurane for 2h. 24h after the end of anesthesia, 6 mice from each group were used Morris water maze to test the spatial learning and memory ability of the mice. Other mice took fresh hippocampal tissue by decapitation and prepared it into a homogenate, and detected b-amyloid peptide (Aβ) aggregation (Aβ, Aβ1-40, Aβ1-42) by Western blot. The phosphorylation of Tau protein and the changes in the phosphorylation level of its sites (serine 396, serine 262, threonine 231) were detected, and the mitochondrial apoptosis signaling pathway genes, including B lymphocyte tumors, were detected by Real-time PCR technology -2 gene (BcL-2), BcL-2-related X protein (Bax) and Caspase-3 (Caspase-3) expression changes.
Results The Morris water maze experiment showed that sevoflurane has no effect on the learning and memory ability of mice, but it has potential neurotoxicity in mice; Jujube saponins can reduce Aβ aggregation and Tau protein phosphorylation in three-transformed model mice; Compared with the three-turn model anesthesia group, BcL-2 expression in the three-turn model administration group decreased, and the expression of Bax and Caspase-3 increased.
Conclusion Jujube saponins can alleviate the apoptotic signaling pathways related to sevoflurane anesthesia activation of mitochondria, reduce Aβ aggregation, reduce Tau protein phosphorylation, and inhibit the apoptosis of mouse hippocampal neurons.