七氟醚对老龄大鼠海马Tau蛋白磷酸化及认知功能的影响  

Effects of Sevoflurane on Hippocampal Tau Phosphorylation and Cognitive Functionin Aged Rats

作　　者：周绪锋[1] 周涛[1] 张明生[1] 

机构地区：[1]江西省人民医院麻醉科,南昌330006

出　　处：《南昌大学学报（医学版）》2016年第2期17-20,27,共5页Journal of Nanchang University：Medical Sciences

基　　金：江西省卫生厅科技计划项目(20143017)

摘　　要：目的研究七氟醚对老龄大鼠海马组织Tau蛋白磷酸化及认知功能的影响。方法将40只20月龄的老龄SD大鼠按随机数字表法分为5组:七氟醚Ⅰa组(SⅠa组)、七氟醚Ⅰb组(SⅠb组)、七氟醚Ⅱa组(SⅡa组)、七氟醚Ⅱb组(SⅡb组)和对照组(C组),每组8只。SⅠa、SⅠb组用1.5%七氟醚分别麻醉2、12h,SⅡa、SⅡb组用3%七氟醚分别麻醉2、12h,C组暴露于纯氧中2h。于麻醉前及麻醉后行Morris水迷宫测试大鼠的认知功能;而后取海马脑组织,HE染色观察细胞核形态的改变,放免法测定脑组织内的GSK-3β和PKA激酶的浓度,免疫印记法测定海马区Tau蛋白的磷酸化水平。结果 SⅠb、SⅡb组麻醉后潜伏期均较麻醉前及SⅠa、SⅡa、C组麻醉后明显延长(P<0.05),SⅡb组麻醉后潜伏期较SⅠb组延长更为显著(P<0.05)。SⅠa、SⅡa、SⅠb、SⅡb组GSK-3β和PKA激酶水平均较C组显著上升(P<0.05);其中SⅠb组显著高于SⅠa组,SⅡb组显著高于SⅡa组,SⅡb组显著高于SⅠb组,SⅡa组显著高于SⅠa组,差异均有统计学意义(P<0.05)。SⅡa、SⅠb、SⅡb组Tau-pSer396磷酸化水平均较C组显著上升(P<0.05);其中SⅠb组显著高于SⅠa组,SⅡb组显著高于SⅡa组,SⅡb组显著高于SⅠb组,差异均有统计学意义(P<0.05)。SⅠa、SⅡa、SⅠb、SⅡb组Tau-pSer262磷酸化水平均较C组显著上升(P<0.05);其中SⅠb组显著高于SⅠa组,SⅡb组显著高于SⅡa组,差异均有统计学意义(P<0.05)。C组海马区细胞形态及分布正常;七氟醚各组可见细胞间隙增宽,细胞数目减少,其中SⅠb、SⅡb组部分细胞出现形态学改变,胞核固缩、浓染甚至破裂。结论七氟醚可通过激活GSK-3β和PKA激酶,使老龄大鼠Tau蛋白(Tau-pSer396、Tau-pSer262)产生一定程度的磷酸化,改变脑细胞的形态,对其认知功能发生一定的影响。Objective To investigate the effects of sevoflurane on hippocampal tau phosphorylation and cognitivefunction in aged rats.Methods Forty 20-month-old SD rats were randomly divided into five groups,with 8rats in each group.The groups SⅠa and SⅠb were given 1.5%sevoflurane anesthesia for 2and 12 hours,respectively.The groups SⅡa and SⅡb were given 3%sevoflurane anesthesia for 2and 12 hours,respectively.The controls（group C）were exposed to pure oxygen for 2hours.The cognitivefunction was assessed by Morris water maze test before and after anesthesia.Rats were sacrificed after Morris water maze test and hippocampal tissues were removed.Themorphological changes in hippocampal neuronswere observed by HE staining.The contents of GSK-3βand PKA in hippocampus were measured by radioimmunoassay.The levels of tau phosphorylation were determined by Western blot.Results Groups SⅠb and SⅡb,the latency was prolonged after anesthesia（P〈0.05）.Furthermore,compared with groups SⅠa,SⅡa and C,the latency was prolonged in groups SⅠb and SⅡb,especially in group SⅡb（P〈0.05）.Compared with group C,the levels of GSK-3βand PKA and expression of phospho-tau Ser262（tau-pSer262）were increased in groups SⅠa,SⅡa,SⅠb and SⅡb and the expression of phospho-tau Ser396（tau-pSer396）was increased in groups SⅡa,SⅠb and SⅡb in a dose-and time-dependent manner（P〈0.05）.The group C showed normal cellular morphology and distribution in the hippocampus.However,sevoflurane anesthesia resulted in dilated intercellular spaces and decreased number of cells.In groups SⅠb and SⅡb,some cells showed nuclear pyknosis,condensation and fragmentation.Conclusion Sevoflurane can affect the cognitive function of aged rats through activating the GSK-3βand PKA,increasing the expression of tau-pSer396 and tau-pSer262,and changing the morphology of brain cells.

关 键 词：七氟醚 TAU蛋白磷酸化 认知功能 动物 实验 大鼠 

分 类 号：R-332[医药卫生] R338.64