丙泊酚复合七氟烷麻醉对轻度认知功能障碍大鼠海马GABA A受体α1/α2亚基稳态的影响  

Effect of propofol combined with sevoflurane anesthesia on GABAA receptorα1/α2 subunit homeostasis in hippocampus of rats with mild cognitive impairment

作　　者：李冬雪 王海云[1] 王金鑫[1] 杨陈祎 Li Dongxue;Wang Haiyun;Wang Jinxin;Yang Chenyi(The Third Central Clinical College of Tianjin Medical University Department of Anesthesiology,Tianjin Third Central Hospital Nankai University Affinity the Third Central Hospital Tianjin Institute of Hepatobiliary Disease Tianjin Key Laboratory of Artificial Cell,300170 Tianjin,China)

机构地区：[1]天津医科大学三中心临床学院,天津市第三中心医院麻醉科,南开大学附属第三中心医院,天津市肝胆疾病研究所,天津市人工细胞重点实验室,300170

出　　处：《中华麻醉学杂志》2020年第6期672-675,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金(81571054);天津市科技支撑重点项目(18YFZCSY00530)。

摘　　要：目的:评价丙泊酚复合七氟烷麻醉对轻度认知功能障碍(MCI)大鼠海马GABA A受体(GABA AR)α1/α2亚基稳态的影响。方法:清洁级健康雄性SD大鼠,16~18月龄,体重450~550 g,采用结扎双侧颈总动脉的方法建立MCI模型。造模后30 d时采用Morris水迷宫实验筛选造模成功的MCI大鼠。取造模成功的MCI大鼠72只,采用随机数字表法分为4组(n=18):假手术组(Sham组)、七氟烷麻醉组(S组)、丙泊酚麻醉组(P组)和丙泊酚复合七氟烷麻醉组(SP组)。S组吸入3%七氟烷3 h;P组静脉输注丙泊酚40 mg·kg^-1·h^-1 3 h;SP组吸入1.7%七氟烷,同时静脉输注丙泊酚20 mg·kg^-1·h^-1 3 h。S组、P组和SP组行胫骨骨折切开复位内固定术。术后14 d时行Y迷宫实验测试认知功能;采用Western blot法测定海马钾离子-氯离子共转运体2(KCC2)、钠钾氯协同转运蛋白1(NKCC1)、GABA ARα1和GABA ARα2的表达水平。结果:与Sham组比较,S组和P组N臂停留时间百分比降低,海马KCC2和GABA ARα1表达下调,NKCC1和GABA ARα2表达上调(P<0.05),SP组上述各指标差异无统计学意义(P>0.05);与S组或P组比较,SP组N臂停留时间百分比升高,海马KCC2和GABA ARα1表达上调,NKCC1和GABA ARα2表达下调(P<0.05)。结论:丙泊酚复合七氟烷麻醉不加重MCI大鼠术后认知功能障碍的机制可能与其维持海马GABA ARα1/α2亚基稳态有关。Objective To evaluate the effect of propofol combined with sevoflurane anesthesia on GABAA receptor(GABAAR)α1/α2 subunit homeostasis in hippocampus of rats with mild cognitive impairment(MCI).Methods Healthy clean-grade male Sprague-Dawley rats,aged 16^-18 months,weighing 450-550 g,were anesthetized.MCI was induced by ligation of bilateral common carotid arteries after anesthesia.Morris water maze test was used to select the rats with MCI at 30 days after establishment of the model.The rats with MCI were divided into 4 groups(n=18 each)using a random number table method:sham operation group(group Sham),sevoflurane anesthesia group(group S),propofol anesthesia group(group P),and propofol combined with sevoflurane anesthesia group(group SP).The rats inhaled 3%sevoflurane for 3 h in group S.Propofol 40 mg·kg^-1·h^-1 was intravenously infused for 3 h in group P.The rats inhaled 1.7%sevoflurane,and propofol 20 mg·kg^-1·h^-1 was intravenously infused for 3 h simultaneously in group SP.Open reduction and internal fixation was performed after tibial fracture was induced in S,P and SP groups.Y-maze test was performed at 14 days after operation to assess cognitive function.The expression of potassium-chloride cotransporter-2(KCC2),sodium-potassium-chloride cotransporter 1(NKCC1),GABAARα1 and GABAARα2 was determined using Western blot.Results Compared with group Sham,the percentage of time of staying at novel arm was significantly decreased,the expression of hippocampal KCC2 and GABAARα1 was down-regulated,and the expression of NKCC1 and GABAARα2 was up-regulated in S and P groups(P<0.05),and no significant change was found in the parameters mentioned above in group SP(P>0.05).Compared with group S or group P,the percentage of time of staying at novel arm was significantly increased,the expression of hippocampal KCC2 and GABAARα1was up-regulated,and the expression of NKCC1 and GABAARα2 was down-regulated in group SP(P<0.05).Conclusion The mechanism by which propofol combined with sevoflurane anesthesia does not

关 键 词：二异丙酚 麻醉药 吸入 受体 GABA-A 认知功能障碍 

分 类 号：R614[医药卫生—麻醉学]