七氟醚对阿尔茨海默症小鼠模型学习记忆的影响研究

Effects of sevoflurane on learning and memory in mice with Alzheimer's disease

目的探讨七氟醚对阿尔茨海默症(AD)小鼠学习记忆的影响及其作用机制。方法 30只C57BL/6小鼠平均随机分为对照组、模型组和七氟醚组,模型组和七氟醚组给予腹腔注射120 mg/(kg·d) D-半乳糖和90 mg/(kg·d)亚硝酸盐诱导AD模型,连续注射6 w;然后七氟醚组吸入3%七氟醚,持续4 h。Morris水迷宫实验检测各组学习记忆能力及空间探索能力,实时定量PCR检测各组不同脑区突触功能相关分子(GluR1和PSD95)及内质网应激关键分子(GRP78、elF-2和PERK)的表达。结果与模型组比较,七氟醚组的逃避潜伏期和穿越平台次数均增加(P <0.05),平台象限滞留时间和平台象限滞留时间比均降低(P <0.05)。与模型组比较,七氟醚组GluR1和PSD95的表达在海马、前额叶皮层、杏仁核及小脑中均降低(P <0.05),GRP78、eIF-2和PERK的表达均增加(P <0.05);杏仁核中eIF-2和PSD95的表达、前额叶皮层和小脑中PERK的表达,在七氟醚组与模型组间比较无显著差异(P> 0.05)。结论七氟醚可降低AD小鼠的学习记忆功能,其机制可能与影响小鼠各脑区突触功能,使内质网应激增加有关。

Objective To explore the effect of sevoflurane on learning and memory in mice with Alzheimer’s disease(AD) and its mechanism. Methods A total of 30 C57 BL/6 mice were randomly divided into a control group, a model group and a sevoflurane group. The model group and sevoflurane group were given intraperitoneal injection of 120 mg/(kg·d) D-galactose and 90 mg/(kg·d)nitrite to induce AD model for six weeks, and then the sevoflurane group inhaled 3% sevoflurane for four hours. Morris water maze experiment was used to detect the learning and memory ability and spatial exploration ability of each group. Real-time quantitative PCR was used to detect the expression of synaptic function related molecules(GluR1 and PSD95) and endoplasmic reticulum stress key molecules(GRP78, e IF-2 and PERK) in different brain regions of each group. Results Compared with the model group, the escape latency and the number of times crossing the platform in the sevoflurane group increased(P < 0.05), while the ratio between platform quadrant retention time periods decreased(P < 0.05). Compared with the model group, the expression of GluR1 and PSD95 in the sevoflurane group decreased in hippocampus, prefrontal cortex, amygdala and cerebellum(P < 0.05), while the expression of GRP78, e IF-2 and PERK increased(P < 0.05);the expression of eIF-2 and PSD95 in amygdala and PERK in prefrontal cortex and cerebellum showed no significant difference between the sevoflurane group and the model group. Conclusion Sevoflurane can reduce the learning and memory function of AD mice. The mechanism may be related to the effect of sevoflurane on synaptic function of various brain regions and the increase of endoplasmic reticulum stress in AD mice.