右美托咪定通过调控AKAP150减轻异丙酚诱导的发育期大鼠学习记忆障碍  

Dexmedetomidine alleviates propofol induced learning and memory impairment in rats at developmental stage by regulating AKAP150

作　　者：王迪 杨剑 何祥[3] WANG Di;YANG Jian;HE Xiang(College of Anesthesia,Guizhou Medical University,Guiyang 550004,China;不详)

机构地区：[1]贵州医科大学麻醉学院,贵阳550004 [2]贵州医科大学附属医院麻醉科,贵阳550004 [3]贵州省人民医院麻醉科,贵阳550004

出　　处：《实用医学杂志》2024年第12期1619-1624,共6页The Journal of Practical Medicine

基　　金：国家自然科学基金项目(编号:81860234);贵州省科技计划项目(编号:黔科合基础-ZK[2023]一般226)。

摘　　要：目的探讨A激酶锚定蛋白150(AKAP150)在右美托咪定减轻异丙酚诱导致发育期大鼠学习记忆障碍中的作用机制。方法7日龄SD大鼠80只随机分为对照组(Con组)、异丙酚组(Pro组)、右美托咪定预先给药组(DP组)、AKAP150腺病毒+DP组(ADP组),每组20只。Con组注射等容量生理盐水;Pro组注射异丙酚50 mg/kg(共2次);DP组注射右美托咪定25μg/kg+异丙酚50 mg/kg;ADP组予腺病毒构建AKAP150敲除模型。水迷宫检测大鼠行为学变化,Western blot法检测海马组织AKAP150、PKA、NLRP3、GSDMD、IL-1β、IL-18表达水平,透射电镜观察海马组织超微结构变化。结果异丙酚处理后的海马组织细胞膜破裂,形成孔道,AKAP150、PKA表达下调(P<0.05),NLRP3、GSDMD、IL-1β、IL-18表达上调(P<0.05),穿越平台次数减少(P<0.05);右美托咪定预给药后的大鼠海马组织细胞膜结构基本正常,AKAP150、PKA表达上调(P<0.05),NLRP3、GSDMD、IL-1β、IL-18表达下调(P<0.05),穿越平台次数增多(P<0.05)。结论右美托咪定可能通过激活AKAP150表达,使PKA活性增强,抑制NLRP3、GSDMD、IL-1β、IL-18表达来减轻异丙酚诱导的发育期大鼠海马组织细胞焦亡,并改善其学习记忆障碍。Objective To explore the mechanism of A kinase anchor-protein 150(AKAP150)in alleviating learning and memory impairment induced by propofol in rats at developmental stage.Methods 80 SD rats aged 7 days were randomly divided into a control group(Con group),propofol group(Pro group),dexmedetomidine pre-administration group(DP group),and AKAP150 adenovirus plus DP group(ADP group)(n=20).The Con group was injected with equal volume normal saline.The Pro group was injected with propofol of 50 mg/kg twice,and the DP group was injected with dexmedetomidine of 25μg/kg plus propofol of 50 mg/kg.The ADP group was treated with adenovirus to construct an AKAP150 knockout model.Expression levels of AKAP150,PKA,NLRP3,GSDMD,IL-1β and IL-18 in hippocampus were detected by Western blot.The ultrastructure of hippocampus was observed by transmission electron microscopy.Results After propofol treatment,hippocampal cell membrane split and pores formed,expressions of AKAP150 and PKA were down-regulated(P<0.05),while expressions of NLRP3,GSDMD,IL-1β and IL-18 were up-regulated(P<0.05),and the frequency of crossing the platform was decreased(P<0.05).After pre-administration of dexmedetomidine,the cell membrane structure of hippocampus was basically normal,expressions of AKAP150 and PKA were up-regulated(P<0.05),expressions of NLRP3,GSDMD,IL-1β and IL-18 were down-regulated(P<0.05),and the frequency of crossing the platform was increased(P<0.05).Conclusions Dexmedetomidine may enhance the activity of PKA and inhibit expressions of NLRP3,GSDMD,IL-1β and IL-18 by activating expression of AKAP150,thereby alleviating propofol-induced pyroptosis in hippocampal tissues and improving learning and memory impairment in rats at developmental stage.

关 键 词：右美托咪定 异丙酚 A激酶锚定蛋白150 学习记忆 细胞焦亡 

分 类 号：R614[医药卫生—麻醉学]