艾司氯胺酮对术后认知功能障碍老龄大鼠海马神经元程序性坏死的影响  

Effect of esketamine on hippocampal neuronal necroptosis in aged rats with postoperative cognitive dysfunction

作　　者：于丽丽[1] 赵娟[2] 尹春平 于家旭 李伟[4] 王旭鹏 周琦 张琦 王秋筠[4] Yu Lili;Zhao Juan;Yin Chunping;Yu Jiaxu;Li Wei;Wang Xupeng;Zhou Qi;Zhang Qi;Wang Qiujun(Department of Anesthesiology,Cangzhou Central Hospital,Cangzhou 061000,China;Experimental Centre for Teaching of Hebei Medical University,Shijiazhuang 050011,China;Department of Anesthesiology,The First Hospital of Hebei Medical University,Shijiazhuang 050030,China;Department of Anesthesiology,The Third Hospital of Hebei Medical University,Shijiazhuang 050051,China;Department of Anesthesiology,Hebei Children′s Hospital,Shijiazhuang 050030,China)

机构地区：[1]沧州市中心医院麻醉科,沧州061000 [2]河北医科大学教学实验中心,石家庄050017 [3]河北医科大学第一医院麻醉科,石家庄050030 [4]河北医科大学第三医院麻醉科,石家庄050051 [5]河北省儿童医院麻醉科,石家庄050031

出　　处：《中华麻醉学杂志》2023年第8期957-961,共5页Chinese Journal of Anesthesiology

摘　　要：目的:评价艾司氯胺酮对术后认知功能障碍老龄大鼠海马神经元程序性坏死的影响。方法:SPF级健康雄性SD大鼠120只,月龄22月,体质量550~600 g,采用随机数字表法分为4组(n=30):对照组(C组)、术后认知功能障碍组(P组)、术后认知功能障碍+艾司氯胺酮组(PE组)和艾司氯胺酮组(CE组)。P组和PE组大鼠在七氟烷麻醉下接受剖腹探查术,术毕分别腹腔注射艾司氯胺酮10 mg/kg和等量0.9%氯化钠注射液,1次/d,连续6 d。CE组和C组不给予麻醉手术处理,分别腹腔注射艾司氯胺酮10 mg/kg和等量0.9%氯化钠注射液,1次/d,连续6 d。4组大鼠于术后7 d时行Morris水迷宫实验,记录逃避潜伏期、穿越原平台位置次数和原平台所在象限停留时间;水迷宫实验结束后,处死大鼠取海马组织,采用流式细胞术测定海马神经元程序性坏死率和胞浆Ca^(2+)浓度;采用Western blot法检测混合谱系激酶结构域样蛋白(MLKL)、磷酸化MLKL(p-MLKL)、受体相互作用蛋白3(RIPK3)、磷酸化RIPK3(p-RIPK3)、RIPK1和磷酸化RIPK1(p-RIPK1)的表达。结果:与C组比较,P组和PE组逃避潜伏期延长,穿越原平台位置次数减少,原平台所在象限停留时间缩短,海马神经元程序性坏死率和胞浆Ca^(2+)浓度升高,海马组织MLKL、p-MLKL、RIPK3、p-RIPK3、RIPK1和p-RIPK1表达上调(P<0.05);与P组比较,PE组逃避潜伏期缩短,穿越原平台位置次数增加,原平台所在象限停留时间延长,海马神经元程序性坏死率和胞浆Ca^(2+)浓度降低,海马组织MLKL、p-MLKL、RIPK3、p-RIPK3、RIPK1和p-RIPK1表达下调(P<0.05)。结论:艾司氯胺酮减轻老龄大鼠术后认知功能障碍的机制可能与抑制海马神经元程序性坏死有关。Objective To evaluate the effect of esketamine on hippocampal neuronal necroptosis in aged rats with postoperative cognitive dysfunction.Methods One hundred and twenty SPF-grade healthy male Sprague-Dawley rats,aged 22 months,weighing 550-600 g,were divided into 4 groups(n=30 each)using a random number table method:control group(group C),postoperative cognitive dysfunction group(group P),postoperative cognitive dysfunction+esketamine group(group PE),and esketamine group(group CE).Rats received exploratory laparotomy under sevoflurane anesthesia,and esketamine 10 mg/kg and the equal volume of 0.9%sodium chloride were intraperitoneally injected at the end of surgery once a day for 6 consecutive days in group P and group PE,respectively.Rats received no anesthesia and surgery,and esketamine 10 mg/kg and the equal volume of 0.9%sodium chloride were intraperitoneally injected at the end of surgery once a day for 6 consecutive days in group CE and group C,respectively.Morris water maze test was performed at 7th day after surgery.The escape latency,times of crossing the original platform and time spent in the original platform quadrant were recorded.The rats were sacrificed at the end of Morris water maze test,and the hippocampal tissues were collected for determination of the rate of necroptosis and cytosolic Ca^(2+) concentrations(by flow cytometry)and expression of mixed lineage kinase domain-like protein(MLKL),phosphorylated MLKL(p-MLKL),receptor-interacting protein kinase-3(RIPK3),phosphorylated RIPK3(p-RIPK3),receptor-interacting protein kinase-1(RIPK1)and phosphorylated RIPK1(p-RIPK1)(by Western blot).Results Compared with group C,the escape latency was significantly prolonged,the times of crossing the original platform were decreased,the time spent in the original platform quadrant was shortened,the necroptosis rate of hippocampal neurons and cytosolic Ca^(2+) concentrations were increased,and the expression of MLKL,p-MLKL,RIPK3,p-RIPK3,RIPK1 and p-RIPK1 was up-regulated in group P and group PE(P<0.05).Compared

关 键 词：氯胺酮 认知功能障碍 老年人 海马 神经元 坏死 

分 类 号：R614[医药卫生—麻醉学]