乳化异氟醚对大鼠认知功能的影响

目的 评价乳化异氟醚对大鼠认知功能的影响.方法 成年雄性SD大鼠72只,8周龄,体重250 ～ 300 g,采用随机数字表法,将其随机分为3组:正常对照组(C组,n=12)、脂肪乳组(E组,n=12)和8％乳化异氟醚组(EI组,n=48).E组于给药后2h时进行水迷宫实验,EI组分别于给药后2h、1、7、14 d时取12只大鼠,进行水迷宫实验,记录逃避潜伏期、平台象限停留时间、穿过平台次数和游泳速度.每个时点水迷宫实验结束后,每组取6只大鼠,取眼眶血,测定血浆皮质醇浓度；然后处死大鼠,取海马组织,测定脑源性神经营养因子(BDNF)和神经生长因子(NGF)的含量；每组取剩余的6只大鼠,取脑组织,测定海马DG区、CA3区、CA2区和CA1区BDNF和NGF表达水平.结果 与C组比较,EI组给药后2h时逃避潜伏期延长,平台象限停留时间缩短,海马DG区和CA3区BDNF表达下调,给药后2h、1d时海马组织BDNF含量降低(P＜0.05或0.01)；与给药后2h时比较,EI组给药后7、14 d时逃避潜伏期缩短,平台象限停留时间延长,给药后1、7、14 d时海马组织NGF含量升高,给药后1d时海马DG区和CA3区BDNF表达上调(P＜0.05或0.01)；E组与C组上述指标比较差异无统计学意义(P＞0.05)；三组血浆皮质醇浓度比较差异无统计学意义(P＞0.05).结论 乳化异氟醚可导致大鼠一过性认知功能障碍,其机制与下调海马BDNF表达有关,而与皮质醇和NGF无关.

Effect of emulsified isoflurane on cognitive function in rats

Objective To evaluate the effect of emulsified isoflurane on cognitive function in rats.Methods Seventy-two adult male SD rats,aged 8 weeks,weighing 250-300 g,were randomly divided into 3 groups:normal control group (group C,n =12),intralipid group(group E,n =12),and 8％ emulsified isoflurane group ( group EI,n =48).Morris water maze test was performed at 2 h after administration in group E and at 2 h,1,7,14 d after administration in 12 rats at each time point in group EI.The escape latency,staying time at the original platform quadrant,frequency of crossing the original platform and swimming speed were recorded.Orbital blood samples were taken from 6 rats in each group after water maze test for determination of the plasma corticosterone concentration,and then the animals were sacrificed and their hippocampi were removed for determination of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) contents.Brains were removed from another 6 rats in each group after water maze test for determination of the expression of BDNF and NGF in DG,CA3,CA2,CA1 of hippocampus.Results Compared with group C,in group EI the escape latency at 2 h after administration was prolonged,staying time at the original platform quadrant was shortened,the expression of BDNF in DG and CA3 of hippocampus was down-regulated and the BDNF content in hippocampus was decreased at 2 h and 1 d after administration( P ＜ 0.05 or 0.01).The escape latency was shortened and staying time at the original platform quadrant was prolonged at 7 and 14 d after administration,the content of NGF in hippocampus was increased at 1,7 and 14 d after administration and the expression of BDNF in DG and CA3 of hippocampus was up-regulated at 1d after administration as compared with those at 2 h after administration in group E1( P ＜ 0.05 or 0.01).There was no significant difference in the variables mentioned above between groups E and C( P ＞ 0.05 ).There was no significant difference in plasma corticosterone concentration among the 3 groups ( P ＞ 0.01 ).Conclusion The mechanism by which emulsified isoflurane results in transient cognitive impairment in rats is related to down-regulating the expression of BDNF in hippocampus,but not related to corticosterone and NGF.