七氟烷复合丙泊酚麻醉对轻度认知功能障碍大鼠术后海马突触可塑性的影响:与KCC2/NKCC1的关系  

Effects of sevoflurane combined with propofol anesthesia on synaptic plasticity in hippocampus after operation in rats with mild cognitive impairment:relationship with KCC2/NKCC1

作　　者：冯路旸 王海云[1] 马纪 汪强 杨陈祎 Feng Luyang;Wang Haiyun;Ma Ji;Wang Qiang;Yang Chenyi(The Third Central Clinical College of Tianjin Medical University Department of Anesthesiology,Tianjin Third Central Hospital Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases Artificial Cell Engineering Technology Research Center Tianjin Institute of Hepatobiliary Disease,Tianjin 300170,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,天津市重症疾病体外生命支持重点实验室,天津市人工细胞工程技术研究中心,天津市肝胆研究所,300170

出　　处：《中华麻醉学杂志》2021年第6期690-694,共5页Chinese Journal of Anesthesiology

基　　金：天津市科技支撑计划重点项目(18YFZCSY00530)。

摘　　要：目的:评价七氟烷复合丙泊酚麻醉对轻度认知功能障碍(MCI)大鼠术后海马突触可塑性的影响及其与钾离子-氯离子共转运体2(KCC2)/钠离子-钾离子-氯离子共转运体1(NKCC1)的关系。方法:雄性SD大鼠,16~18月龄,体重440~540 g,采用双侧颈总动脉重度狭窄建立MCI模型。取MCI模型制备成功的大鼠48只,采用随机数字表法分为4组(n=12):假手术组(Sham组)、七氟烷麻醉组(S组)、丙泊酚麻醉组(P组)和七氟烷复合丙泊酚麻醉组(SP组)。S组、P组、SP组行胫骨骨折切开复位内固定术,麻醉方法:SP组吸入1.7%七氟烷复合静脉输注丙泊酚20 mg·kg^(-1)·h^(-1)3 h,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。术后14 d行新异物体实验,计算新异物体识别指数。术后19 d行在体电生理实验,测定长时程增强的场兴奋性突触后电位(fEPSP)幅值,采用Western blot法测定海马KCC2和NKCC1的表达水平,计算KCC2/NKCC1比值。术后30 d行Golgi-Cox染色,计算海马CA1区树突棘密度。结果:与Sham组比较,S组和P组新异物体识别指数、海马KCC2/NKCC1比值、CA1区突触棘密度和fEPSP幅值降低(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组新异物体识别指数、海马KCC2/NKCC1比值、CA1区突触棘密度和fEPSP幅值升高(P<0.05)。结论:七氟烷复合丙泊酚麻醉不加重MCI大鼠术后认知功能障碍可能与维持海马KCC2/NKCC1平衡,改善海马突触可塑性有关。Objective To evaluate the effects of sevoflurane combined with propofol anesthesia on the synaptic plasticity in the hippocampus after operation in rats with mild cognitive impairment(MCI)and the relationship with potassium-chloride cotransporter-2(KCC2)/sodium-potassium-chloride cotransporter 1(NKCC1).Methods Clean-grade healthy male Sprague-Dawley rats,aged 16-18 months,weighing 440-540 g,in which MCI was induced by severe bilateral common carotid artery stenosis(BCAS).Forty-eight rats with MCI were divided into 4 groups(n=12 each)using a random number table method:sham operation group(group Sham),sevoflurane anesthesia group(group S),propofol anesthesia group(group P),and sevoflurane and propofol anesthesia group(group SP).After disappearance of eyelash reflex,open reduction and internal fixation was performed after tibial fracture was induced in S,P and SP groups.Anesthesia method was as follows:1.7%sevoflurane was inhaled and propofol 20 mg·kg^(-1)·h^(-1) was intravenously infused for 3 h in group SP,3%sevoflurane was inhaled for 3 h in group S,and propofol was intravenously infused at rate of 40 mg·kg^(-1)·h^(-1) for 3 h in group P.The novel object recognition(NOR)test was performed at 14 days after operation,and the discrimination index in NOR test was calculated.The in vivo electrophysiological experiment was performed on 19 days after operation to measure long-term potentiation and amplitude of the field excitatory postsynaptic potential(fEPSP).The expression of KCC2 and NKCC1 was determined by Western blot,and the ratio of KCC2/NKCC1 was calculated.The density of dendritic spines in the hippocampal CA1 region was determined by Golgi-COX staining performed at 30 days after operation.Results Compared with Sham group,the discrimination index in NOR test,hippocampal KCC2/NKCC1 ratio,density of dendritic spines in hippocampal CA1 region,and amplitude of fEPSP were significantly decreased 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).Co

关 键 词：二异丙酚 麻醉药 吸入 认知功能障碍 神经元可塑性 协同转运蛋白 

分 类 号：R614[医药卫生—麻醉学]