Changes of CaM-CaMK-CREB signaling pathway and related neuron factors in hippocampus of rats after sevoflurane and propofol administration

Y.-Z. Ling, X.-W. Zhang, X. Wang, Y. Du, L. Yu

Department of Anesthesiology, The First Affiliated Hospital of Bengbu Medical College, Bengbu City, Anhui Province, China. yuli95@163.com

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• Pharmacology

OBJECTIVE: To investigate the changes of CaM-CaMK-CREB signaling pathway and related neuron factors in hippocampus of rats after sevoflurane and propofol administration.

MATERIALS AND METHODS: A total of 90 SD rats, half male and half female, were selected. They were randomized into anesthesia group (AG) and control group (CG), in which 30 rats under propofol anesthesia in the AG were included in group A, 30 rats under sevoflurane anesthesia were included in group B, and 30 rats under mixed ventilation of air and oxygen were included in the CG. Before (10 rats were killed in each group) and at the end of anesthesia (2 weeks of anesthesia and 7 days of Morris water maze test), rats were respectively killed and then an appropriate amount of hippocampus was separated. Human tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), calmodulin (CaM), calmodulin-dependent kinase Ⅱ a (CaMK II a), NMDA receptor 2B (NR2B), cysteine aspartate specific protease-3 mRNA (Caspase-3mRNA) and protein contents were detected.

RESULTS: The latency of rats in group A and group B, as well as their times of crossing the original platform on 1, 4, and 7d were markedly higher than those of the CG, and those in group B were markedly lower than those in group A (p<0.001). The total distance of rats in group A and group B on 1, 4, and 7d was significantly higher than that of the CG, and that in group B was dramatically lower than that in group A (p<0.001). The speed of rats in the three groups ranged from 1d to 7d, and there was no significant difference at different time points (p>0.05). At the end of anesthesia, the expression levels of CaM mRNA and protein in hippocampus of rats in group A and group B were remarkably higher than those of the CG, and those of CaMK II a mRNA and protein were remarkably lower than those of the CG; the CaM mRNA and protein expression levels in hippocampus of group A were significantly higher than those of group B, and those of CaMK IL a mRNA and protein were significantly lower than those of group B (p<0.001). Simultaneously, the expression levels of NR2BmRNA, Caspase-3mRNA and protein in hippocampus of group A and group B were substantially higher than those of the CG, and those in group B were substantially lower than those in group A (p<0.001). What’s more, the TNF-a and VEGF expression levels in hippocampus of group A and B were markedly higher than those of the CG, and those in group B were dramatically lower than those of group A (p<0.001).

CONCLUSIONS: Sevoflurane anesthesia on the CaM-CaMK-CREB signaling pathway and learning and memory function of rats is less volatile, which does better in safeguarding stability.

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