α-酮戊二酸对老龄小鼠术后谵妄的影响  

Effect ofα-ketoglutarate on postoperative delirium in aged mice

作　　者：羊妍[1] 薄靳华[1] 刘玥[1] 杨帅 张伟[1] 顾小萍[1] 马正良[1] Yang Yan;Bo Jinhua;Liu Yue;Yang Shuai;Zhang Wei;Gu Xiaoping;Ma Zhengliang(Department of Anesthesiology,Affiliated Drum Tower Hospital of Medical School of Nanjing University,Nanjing 210008,China)

机构地区：[1]南京大学医学院附属鼓楼医院麻醉科,210008

出　　处：《中华麻醉学杂志》2021年第4期440-444,共5页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金(81771142)。

摘　　要：目的评价α-酮戊二酸对老龄小鼠术后谵妄的影响。方法雄性C57BL/6N小鼠80只,18月龄,体重30~35 g,采用随机数字表法分为4组(n=20):对照+溶剂组(C组)、对照+α-酮戊二酸组(C+AKG组)、手术+溶剂组(S组)和手术+α-酮戊二酸组(S+AKG组)。C+AKG组和S+AKG组分别于术前连续3 d腹腔注射α-酮戊二酸二甲酯0.6 mg/kg;C组和S组于相同时点腹腔注射等容量生理盐水。在异氟烷麻醉下进行剖腹探查术制备小鼠术后谵妄模型。分别于术前24 h和术后6、9、24 h时进行食物埋藏试验(进食潜伏期)、旷场试验(总运动距离、进入中央区潜伏期、中央区停留时间和凝滞时间)和Y迷宫试验(进入新异臂时间和次数)。术后6 h时处死小鼠,取海马组织,采用免疫荧光染色法测定小胶质细胞标志物离子钙结合接头分子1(Iba-1)的表达和阳性细胞计数,Western blot法检测海马IL-1β与TNF-α表达。结果与C组比较,S组术后各时点进食潜伏期延长,术后6和9 h时进入中央区潜伏期延长,中央区停留时间缩短,术后6、9和24 h凝滞时间缩短,术后6和9 h时新异臂进入次数减少,术后6 h时新异臂停留时间缩短,海马Iba-1表达上调,Iba-1阳性细胞计数增加,IL-1β与TNF-α表达上调(P<0.05),C+AKG组术后各时点行为学指标差异无统计学意义(P>0.05);与S组比较,S+AKG组术后各时点进食潜伏期缩短,术后9 h时进入中央区潜伏期缩短,术后6和9 h时中央区停留时间延长,术后9和24 h时凝滞时间延长,术后9 h时新异臂进入次数增加,海马Iba-1表达下调,Iba-1阳性细胞计数减少,IL-1β与TNF-α表达下调(P<0.05)。结论α-酮戊二酸可减轻老龄小鼠术后谵妄,其机制可能与抑制小胶质细胞激活,从而减轻炎症反应有关。Objective To evaluate the effect ofα-ketoglutarate(AKG)on postoperative delirium(POD)in aged mice.Methods Eighty male C57BL/6N mice,aged 18 months,weighing 30-35 g,were divided into 4 groups(n=20 each)using a random number table method:control+solvent group(group C),control+AKG group(group C+AKG),surgery+solvent group(group S)and surgery+AKG group(group S+AKG).Dimethyl 2-oxoglutarate 0.6 mg/kg was injected intraperitoneally for 3 consecutive days before surgery in C+AKG and S+AKG groups,while the equal volume of normal saline was given in C and S groups.Exploratory laparotomy was performed under anesthesia with isoflurane to establish POD model.The behaviors of mice in each group were tested at 24 h before surgery and 6,9 and 24 h after surgery using buried food test(the latency to eat food),open field test(total distance,latency to the center,time and freezing time spent in the center)and Y maze test(duration in the novel arm and the number of entries into the novel arm),respectively.Then the animals were sacrificed at 6 h after operation,hippocampal tissues were removed for determination of the expression of microglia-specific marker ionized calcium binding adaptor molecule-1(Iba-1),the number of Iba-1 positive cells(using immunofluorescence staining),and the expression of interleukin-1beta(IL-1β)and tumor necrosis factor-alpha(TNF-α)in hippocamapus(by Western blot).Results Compared with group C,the latency to eat food at eath time point was significantly prolonged,latency to the center at 6 and 9 h after surgery was prolonged,time spent in the center at 6 and 9 h after surgery was shortened,freezing time at 6,9 and 24 h after surgery was shortened,the number of entries into the novel arm at 6 and 9 h after surgery was decreased,duration in the novel arm at 6 h after surgery was shortened,the expression of Iba-1 was up-regulated,the number of Iba-1 positive cells was increased,and the expression of IL-1βand TNF-αin hippocampus was up-regulated in group S(P<0.05),and no significant change was found in the b

关 键 词：酮戊二酸类 谵妄 手术后并发症 老年人 

分 类 号：R614[医药卫生—麻醉学]