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七氟醚和丙泊酚给药后大鼠海马钙调素钙调蛋白激酶-CREB 信号通路及相关神经元因子的变化。

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

机构信息

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

出版信息

Eur Rev Med Pharmacol Sci. 2021 Jan;25(2):957-967. doi: 10.26355/eurrev_202101_24665.

Abstract

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.

摘要

目的

研究七氟醚和丙泊酚麻醉后大鼠海马钙调素-钙调蛋白依赖性激酶-CREB 信号通路及相关神经元因子的变化。

材料与方法

选择 90 只 SD 大鼠,雌雄各半,随机分为麻醉组(AG)和对照组(CG),其中 AG 中 30 只接受丙泊酚麻醉,分为 A 组,30 只接受七氟醚麻醉,分为 B 组,CG 中 30 只接受空气和氧气混合通气,每组各 10 只大鼠在麻醉前(每组各处死 10 只)和麻醉结束时(2 周麻醉和 7 天 Morris 水迷宫测试)处死,然后分离适量海马。检测人肿瘤坏死因子-α(TNF-α)、血管内皮生长因子(VEGF)、钙调蛋白(CaM)、钙调蛋白依赖性激酶Ⅱ a(CaMK II a)、N-甲基-D-天冬氨酸受体 2B(NR2B)、半胱天冬氨酸特异性蛋白酶-3mRNA(Caspase-3mRNA)和蛋白含量。

结果

A 组和 B 组大鼠潜伏期以及 1、4、7d 时穿越原平台次数均明显高于 CG 组,B 组明显低于 A 组(p<0.001);A 组和 B 组大鼠 1、4、7d 总距离明显高于 CG 组,B 组明显低于 A 组(p<0.001);三组大鼠速度在 1~7d 之间变化,不同时间点无显著差异(p>0.05)。麻醉结束时,A 组和 B 组大鼠海马 CaMmRNA 和蛋白表达明显高于 CG 组,CaMK II a mRNA 和蛋白表达明显低于 CG 组;A 组海马 CaMmRNA 和蛋白表达明显高于 B 组,CaMK II a mRNA 和蛋白表达明显低于 B 组(p<0.001)。同时,A 组和 B 组大鼠海马 NR2BmRNA、Caspase-3mRNA 和蛋白表达明显高于 CG 组,B 组明显低于 A 组(p<0.001)。此外,A 组和 B 组大鼠海马 TNF-a 和 VEGF 表达明显高于 CG 组,B 组明显低于 A 组(p<0.001)。

结论

七氟醚麻醉对大鼠 CaM-CaMK-CREB 信号通路及学习记忆功能影响较小,稳定性更好。

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