右美托咪定介导miR-182-5p/BDNF改善肝叶切除术后大鼠早期认知功能障碍的机制研究  

Mechanism of dexmedetomidine in improving early cognitive dysfunction in rats after hepatic lobectomy by regulating miR-182-5p/BDNF

作　　者：陈艳 高晓增 CHEN Yan;GAO Xiaozeng(Department of Anesthesiology,Linxi Hospital of Kailuan General Hospital of Hebei Province,Tangshan,Hebei,063000;the Affiliated Hospital of North China University of Science and Technology,Tangshan,Hebei,063000)

机构地区：[1]河北省开滦总医院林西医院麻醉科,河北唐山063000 [2]华北理工大学附属医院,河北唐山063000

出　　处：《实用临床医药杂志》2024年第19期48-54,共7页Journal of Clinical Medicine in Practice

基　　金：河北省2024年度医学科学研究课题计划(20241642)。

摘　　要：目的探讨右美托咪定(DEX)通过调控微小RNA-182-5p/脑源性神经营养因子(miR-182-5p/BDNF)轴对肝叶切除术后大鼠早期认知功能障碍的影响。方法将60只无特定病原体(SPF)级SD雄性大鼠随机分为对照组、模型组、DEX低剂量组(25μg/kg)、DEX中剂量组(50μg/kg)、DEX高剂量组(100μg/kg)和DEX+miR-182-5p模拟剂组,每组10只。模型组大鼠吸入七氟醚麻醉后行部分肝叶切除术;DEX低、中、高剂量组大鼠预先通过腹腔注射25、50、100μg/kg DEX,30 min后吸入七氟醚麻醉后行部分肝叶切除术;DEX+miR-182-5p模拟剂组大鼠处理方法同DEX高剂量组,术后每2 d通过尾静脉注射miR-182-5p模拟剂(50μg);对照组大鼠通过腹腔注射2 mL/kg生理盐水,并吸入七氟醚进行麻醉2 h。采用Morris水迷宫试验与神经功能缺损评估量表(NSS)评估各组大鼠的术后认知功能与神经功能损伤。采用实时荧光定量聚合酶链反应(qRT-PCR)测定大鼠海马组织中miR-182-5p的水平。采用蛋白质免疫印迹法测定大鼠海马组织中BDNF的蛋白表达水平。采用生物信息学分析miR-182-5p与BDNF的3′UTR的结合区域,并利用双荧光素酶报告基因实验检测miR-182-5p与BDNF的靶向关系。结果与对照组相比,模型组大鼠术后2~5 d的Morris水迷宫测试逃避潜伏期延长,术后1、3、7 d的NSS评分升高;与模型组相比,DEX治疗组大鼠术后2~5 d的Morris水迷宫测试逃避潜伏期缩短,术后3、7 d的NSS评分降低,且呈剂量依赖性;与DEX高剂量组相比,DEX+miR-182-5p模拟剂组术后2~5 d的Morris水迷宫测试逃避潜伏期延长,术后3、7 d的NSS评分升高;与对照组相比,模型组大鼠术后海马组织中miR-182-5p水平升高,BDNF水平降低;与模型组相比,DEX治疗组大鼠术后海马组织中miR-182-5p水平降低,BDNF水平升高,且呈剂量依赖性;与DEX高剂量组相比,DEX+miR-182-5p模拟剂组术后海马组织中miR-182-5p水平升高,BDNF水平降低;上述组间差异均有统计�Objective To investigate the effect of dexmedetomidine(DEX)on early cognitive dysfunction after hepatic lobectomy by regulating microRNA-182-5p/brain-derived neurotrophic factor(miR-182-5p/BDNF)axis in rats.Methods Sixty specific pathogen free(SPF)SD male rats were randomly divided into control group,model group,DEX low dose treatment group(25μg/kg),DEX medium dose treatment group(50μg/kg),DEX high dose treatment group(100μg/kg),and DEX+miR-182-5p mimic group,with 10 rats each group.The rats in the model group were anesthetized with sevoflurane and then underwent partial hepatectomy.The rats in DEX low-,medium-,and high-dose treatment groups were injected with DEX(25,50,and 100μg/kg)intraperitoneally and inhaled sevoflurane for 30 minutes before partial hepatectomy.DEX+miR-182-5p mimic group rats were treated with the same method as DEX high-dose treatment group,and miR-182-5p mimic(50μg)was injected through tail vein every 2 days after operation.Rats in the control group were intraperitoneally injected with 2 mL/kg normal saline,then anesthetized by inhalation of sevoflurane for 2 hours.Morris water maze test and Neurological Severity Scale(NSS)were used to evaluate the postoperative cognitive function and neurological function damage of rats in each group.Quantitative reverse transcription polymerase chain reaction(qRT-PCR)was used to measure the level of miR-182-5p in rat hippocampus.The protein expression level of BDNF in hippocampus was determined by western blot.The binding region of miR-182-5p and BDNF 3'UTR was analyzed by bioinformatics,and the targeting relationship between miR-182-5p and BDNF was detected by dual luciferase reporter gene assay.Results The results showed that compared with the control group,the escape latency of Morris water maze test in the model group was significantly prolonged at 2 to 5 days after operation(P<0.05),and the NSS scores in the model group were significantly increased at 1,3 and 7 d after operation(P<0.05).Compared with the model group,the rats in the DEX treatment

关 键 词：右美托咪定 微小RNA-182-5p 脑源性神经营养因子 肝叶切除术 术后认知功能障碍 

分 类 号：R749.1[医药卫生—神经病学与精神病学] R575[医药卫生—临床医学] R329.2