右美托咪定对老年患者术后早期认知功能障碍保护机制的代谢组学研究  

Protective mechanism of dexmedetomidine on early postoperative cognitive dysfunction in elderly:a metabonomic study

作　　者：杜远琳 佘汉 唐小唪 黄炳强 彭霁 刘良明 李涛 胡弋 DU Yuanlin;SHE Han;TANG Xiaofeng;HUANG Bingqiang;PENG Ji;LIU Liangming;LI Tao;HU Yi(Department of Anesthesiology,Army Medical Center of PLA,Chongqing,400042,China;State Key Laboratory of Trauma,Burns and Combined Injuries,Department of War Wound Shock and Transfusion,Institute of Surgery Research,Army Medical Center of PLA,Chongqing,400042,China)

机构地区：[1]陆军特色医学中心麻醉科,重庆400042 [2]陆军特色医学中心野战外科研究部战伤休克与输血研究室,创伤烧伤与复合伤国家重点实验室,重庆400042

出　　处：《陆军军医大学学报》2023年第20期2120-2131,共12页Journal of Army Medical University

基　　金：国家自然科学基金重点项目(81830065);国家自然科学基金面上项目(82270523);国家自然科学基金青年基金(82300561)。

摘　　要：目的通过对右美托咪定干预后老年患者术后早期认知功能相关代谢物测定,探讨右美托咪定保护术后早期认知功能的作用机理。方法采用随机、单盲、安慰剂对照研究设计方案,选择2022年1-5月陆军特色医学中心关节外科收治关节炎并接受关节置换手术(含髋关节置换术和膝关节置换术)的老年患者48例,其中男性10例,女性38例,平均年龄71.38(65~89)岁。按2∶1比例随机分为右美托咪定组(DEX组)32例和对照组(CON组,以相同的方法等容等速持续泵注0.9%生理盐水)16例。分别在术前、后1天采用简易智力状态检查量表(mini-mental state examination,MMSE)对患者认知功能进行评估。使用超高效液相色谱-四极杆-静电场轨道阱高分辨质谱联用(ultra-high performance liquid chromatography coupled with Q Exactive mass spectrometry,UHPLC-QE-MS)对患者血清样本进行代谢组学分析,筛选差异代谢物及其通路。结果以术后MMSE评分低于术前≥2分判定为POCD,DEX组、CON组发生率分别6.25%、37.5%,2组差异有统计学意义(χ2=5.419,P=0.02)。代谢组学检测出70种差异代谢物,DEX组十二酸乙酯、前列腺素D2、硫酸吲哚氧基、表油菜素内酯、二酰基甘油(18∶4/15∶0/0∶0)、甘油三酯H等明显下调;L-异亮氨酸、正亮氨酸、甜菜碱、3,3,5-三碘-L-酪氨酸-β-D-葡萄糖醛酸苷、磷脂酰胆碱(22∶6/16∶1)、磷脂酰胆碱(22∶5/14∶0)、磷脂酰胆碱(18∶4/18∶1)、脑磷脂(20∶3/14∶1)、甘油磷酸胆碱、L-丝氨酸、γ-氨基丁酸等显著上调;涉及的主要通路有甘油磷脂代谢,氨酰-tRNA生物合成,甘氨酸、丝氨酸和苏氨酸代谢通路,丙氨酸、天冬氨酸和谷氨酸代谢通路等。结论右美托咪定能通过参与脂质代谢、氨基酸代谢等多种生物途径,抑制炎症反应、减轻氧化应激、改善突触结构和功能、调控细胞能量代谢等来保护术后早期认知功能。Objective To investigate the protective mechanism of dexmedetomidine(Dex)on early postoperative cognitive function in the elderly by determining cognitive function-related metabolites during the early postoperative period following intervention.Methods A randomized,single-blind,placebo-controlled study was conducted on 48 elderly patients undergoing joint replacement surgery(including hip and knee replacement surgeries)due to arthritis in Army medical center from January to May 2022.They were 10 males and 38 females,at an average age of 71.38(ranging from 65 to 89)years.They were randomly divided into a Dex group(n=32)and a control group(CON group,receiving 0.9%saline at an equal rate and volume via same way,n=16)in a ratio of 2∶1.Mini-Mental State Examination(MMSE)was performed to evaluate cognitive function before and 1 d after the surgery.Metabolomic analysis was carried out on the serum samples harvested on the day of surgery and 1 d after using ultra-high-performance liquid chromatography-quadrupole-Orbitrap high-resolution mass spectrometry(UHPLC-QE-MS)in order to screen for differential metabolites and their pathways.Results Postoperative cognitive dysfunction(POCD)was defined as a decrease in MMSE score by≥2 points when compared to the preoperative score.The incidence of POCD was 6.25%and 37.5%,respectively,in the Dex group and CON group,with statistical significance(Chi-square=5.419,P=0.02).Metabolomics analysis revealed 70 differential metabolites,including significantly down-regulated compounds such as ethyl dodecanote,prostaglandin D2,Indoxyl sulfate,Epibrassinolide,Diacylglycerol(18∶4/15∶0/0∶0),Ganoderide H.Up-regulated metabolites included,L-Alloisoleucine,L-Norleucine,Betaine,3,3,5-triiodo-L-thyronine-beta-D-glucuronoside,Phosphatidylcholine(22∶6/16∶1),Phosphatidylcholine(22∶5/14∶0),Phosphatidylcholine(18∶4/18∶1),Cephalin(20∶3/14∶1),Glycerophosphocholine,L-Serine,Gamma-Aminobutyric acid.The main pathways involved were glycerophospholipid metabolism,aminoacyl-tRNA biosynthe

关 键 词：代谢组学 右美托咪定 关节置换术 术后早期认知功能障碍 

分 类 号：R749.2[医药卫生—神经病学与精神病学] R966[医药卫生—临床医学] R971.2