七氟烷诱导新生小鼠认知障碍的机制研究  

Mechanism of Sevoflurane-induced Cognitive Impairment in Neonatal Mice

作　　者：董凯 杨智慧 焦勇强 李娜 DONG Kai;YANG Zhihui;JIAO Yongqiang;LI Na(Department of Anesthesiology,Hankuang General Hospital of North China Medical and Health Group,Handan,Hebei 056105,China;the Second Department of Internal Medicine,Hankuang General Hospital of North China Medical and Health Group,Handan,Hebei 056105,China;Department of Orthopedics,Hebei University of Engineering,Handan,Hebei 056105,China)

机构地区：[1]华北医疗健康集团邯矿总医院麻醉科,河北邯郸056105 [2]华北医疗健康集团邯矿总医院内二科,河北邯郸056105 [3]河北工程大学附属医院骨科,河北056105

出　　处：《转化医学杂志》2024年第2期162-168,共7页Translational Medicine Journal

摘　　要：目的 探讨七氟烷诱导新生小鼠术后认知障碍(POCD)作用机制。方法 12只新生小鼠随机分为七氟烷组和对照组各6例。对照组给予吸入60%氧气,七氟烷组给予3%七氟烷(大剂量)加60%氧气。2组每天吸入2 h,持续3 d。使用莫里斯水迷宫实验检测小鼠认知和记忆能力。实验结束后,解剖新生小鼠大脑皮层和海马组织,行病理切片和HE、尼氏染色、TUNEL、透射电镜以观察大脑皮层和海马组织形态变化;应用Western blot及流式细胞术检测细胞凋亡率、海马组织内程序性坏死相关蛋白表达量。结果 与对照组相比,七氟烷组逃逸潜伏期显著延长,穿平台次数减少,目标象限停留时间缩短(P<0.01)。HE染色结果显示,七氟烷组神经元萎缩退变程度及皮质区间质水肿程度强于对照组;尼氏染色结果显示,与对照组相比,七氟烷组神经元萎缩和核溶解现象增多;2组大脑皮质和海马组织萎缩和退化细胞数量及萎缩细胞数量少于对照组(P<0.01)。透射电镜结果表明,与对照组相比,七氟烷组脑细胞损伤严重。与对照组比较,七氟烷组新生小鼠海马组织中GRP78和GRP94蛋白相对表达水平及P22、P47、半胱氨酸天冬氨酸蛋白酶(Caspase)-1、Caspase-3、Caspase-9蛋白相对表达量升高,细胞凋亡率升高(P<0.01)。结论 大剂量七氟烷可以通过诱导POCD新生小鼠海马组织内内质网应激反应,进而诱导海马组织程序性坏死加重病情。Objective To investigate the mechanism of Sevoflurane-induced postoperative cognitive dysfunction(POCD)in neonatal mice.Methods Twelve neonatal mice were randomly divided into Sevoflurane group and control group,with 6 cases in each group.The control group was given 60%oxygen inhalation,and the Sevoflurane group was given 3%Sevoflurane(large dose)plus 60%oxygen.The two groups were inhaled for 2 h a day for 3 days.The Morris water maze test was used to detect the cognitive and memory ability of mice.After the experiment,the cerebral cortex and hippocampal tissues of newborn mice were dissected,and pathological sections,HE,Nissl staining,TUNEL and transmission electron microscopy were performed to observe the morphological changes in the cerebral cortex and hippocampal tissues.Western blot and flow cytometry were used to detect apoptosis rate and protein expression of programmed necrosis in hippocampus.Results Compared with the control group,the escape latency of Sevoflurane group was significantly prolonged,the number of platform crossing was reduced,and the target quadrant residence time was shortened(P<0.01).HE staining showed that the degree of neuronal atrophy and cortical interstitial edema in Sevoflurane group was stronger than that in control group.The results of Nissl staining showed that the neuronal atrophy and nucleolysis were increased in Sevoflurane group compared with the control group,and the number of atrophic and degenerated cells in cerebral cortex and hippocampus tissue as well as the number of atrophic cells in the two groups was lower than that in the control group(P<0.01).The results of transmission electron microscopy showed that the brain cells in Sevoflurane group were more damaged than those in control group.Compared with the control group,the relative expression levels of GRP78 and GRP94 proteins and the relative expression levels of P22,P47,Caspase-1,Caspase-3 and Caspase-9 proteins in hippocampal tissue of neonatal mice in Sevoflurane group as well as apoptosis rate were increased(P<0.

关 键 词：七氟烷 认知障碍 海马 动物行为学 内质网应激 半胱氨酸天冬氨酸蛋白酶1 细胞凋亡 小鼠 C57BL 

分 类 号：R-332[医药卫生] R741