PV中间神经元CypD在七氟烷多次麻醉致新生小鼠远期认知功能障碍的作用  

Role of CypD in parvalbumin interneurons in long-term cognitive dysfunction induced by multiple sevoflurane anesthesia in neonatal mice

作　　者：张晓媛 邹雪竹 王路路 张丽 Zhang Xiaoyuan;Zou Xuezhu;Wang Lulu;Zhang Li(Department of Anesthesiology and Perioperative Medicine,The Second Affiliated Hospital of Anhui Medical University,Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education,Anhui Medical University,Hefei 203601,China;Department of Pediatrics,The Second Affiliated Hospital of Anhui Medical University,Hefei 203601,China)

机构地区：[1]安徽医科大学第二附属医院麻醉与围术期医学科、安徽医科大学麻醉与围术期医学安徽普通高校重点实验室,合肥203601 [2]安徽医科大学第二附属医院儿科,合肥203601

出　　处：《中华麻醉学杂志》2024年第10期1200-1206,共7页Chinese Journal of Anesthesiology

基　　金：安徽省自然科学基金项目(1908085QH358);安徽医科大学第二附属医院国家自然科学青年基金孵育计划(2020GQFY01)。

摘　　要：目的探讨小清蛋白(PV)中间神经元亲环素D(CypD)在七氟烷多次麻醉致新生小鼠远期认知功能障碍的作用。方法选取6日龄SPF级健康PVCre小鼠与PpifF/F-PVCre小鼠各32只, 采用随机数字表法将上述小鼠分为4组(n=16):PVCre小鼠对照组(Con组)、PVCre小鼠七氟烷组(Sevo组)、PpifF/F-PVCre小鼠对照组(CKO-Con组)和PpifF/F-PVCre小鼠七氟烷组(CKO-Sevo组)。Sevo组与CKO-Sevo组于出生后6、7和8 d, 连续3 d使用3%七氟烷麻醉2 h;Con组与CKO-Con组于相应时点吸入30%氧气和70%空气的混合气体2 h。于小鼠出生后第42天, 采用新物体识别实验和Morris水迷宫实验测定4组小鼠学习记忆能力。行为学实验结束后处死小鼠取海马组织, 采用Western blot法检测海马PV、CypD和突触后致密物95(PSD95)表达, 测定线粒体膜电位(MMP)和活性氧(ROS)活性。结果与Con组比较, Sevo组新物体识别指数下降, 逃避潜伏期延长, 原平台象限停留时间缩短, 穿越原平台位置次数减少, MMP下降, ROS活性升高, 海马CypD表达上调, PV和PSD95表达下调(P<0.05);与Sevo组比较, CKO-Sevo组新物体识别指数升高, 逃避潜伏期缩短, 原平台象限停留时间延长, 穿越原平台位置次数增多, MMP升高, ROS活性下降, 海马CypD表达下调, PV和PSD95表达上调(P<0.05);Con组、CKO-Con组和CKO-Sevo组小鼠新物体识别指数、逃避潜伏期、原平台象限停留时间、穿越原平台位置次数、MMP、ROS活性、PV和PSD95表达差异无统计学意义(P>0.05)。结论 PV中间神经元CypD表达上调参与了七氟烷多次麻醉诱发新生小鼠远期认知功能障碍的过程。Objective:To investigate the role of cyclophilin D(CypD)in parvalbumin(PV)interneurons in long-term cognitive dysfunction induced by multiple sevoflurane anesthesia in neonatal mice.Methods:Thirty-two specific pathogen-free healthy PV Cre mice and 32 specific pathogen-free healthy Ppif F/F-PV Cre mice,aged 6 days,were selected and divided into 4 groups(n=16 each)using a random number table method:control group of PV Cre mice(Con group),sevoflurane exposure group of PV Cre mice(Sevo group),control group of Ppif F/F-PV Cre mice(CKO-Con group),and sevoflurane exposure group of Ppif F/F-PV Cre mice(CKO-Sevo group).Sevo group and CKO-Sevo group were exposed to 3%sevoflurane for 2 h from the 6th day to the 8th day,while Con group and CKO-Con group inhaled a mixture of 30%O 2 and 70%air for 2 h at the corresponding time points.On the 42th day of age,the learning and memory abilities of mice in all four groups were evaluated using the novel object recognition test and Morris water maze test.After conducting behavioral experiments,the mice were sacrificed,and hippocampal tissues were collected to determine the expression of PV,CypD,and postsynaptic density protein-95(PSD95)in the hippocampus(by Western blot)and to measure the mitochondrial membrane potential(MMP)and activity of reactive oxygen species(ROS).Results:Compared to Con group,the novel object recognition index was significantly decreased,the escape latency was prolonged,the time of staying at the original platform quadrant was shortened,the number of crossing the original platform was reduced,the MMP was decreased,the activity of ROS was increased,the expression of CypD was up-regulated,and the expression of PV and PSD95 was down-regulated in Sevo group(P<0.05).Compared to Sevo group,the novel object recognition index was significantly increased,the escape latency was shortened,the time of staying at the original platform quadrant was prolonged,the number of crossing the original platform was increased,MMP was increased,the activity of ROS was decreased,the expr

关 键 词：小白蛋白 亲环素D 麻醉 吸入 认知功能障碍 

分 类 号：R614[医药卫生—麻醉学]