右美托咪定对新生大鼠七氟醚麻醉后远期感觉运动门控系统的影响

Effect of dexmedetomidine on long-term sensorimotor gating system after sevoflurane anaesthesia in neonatal rats

目的评价右美托咪定对新生大鼠七氟醚麻醉后远期感觉运动门控系统的影响.方法清洁健康雄性SD大鼠144只,4~6日龄,体重8~15 g,采用随机数字表法分为4组(n=36):对照组(C组)、七氟醚组(S组)、右美托咪定+七氟醚组(D+S组)和右美托咪定+α2受体拮抗剂阿替美唑+七氟醚组(D+A+S组).S组采用6%七氟醚诱导麻醉3 min,2.1%七氟醚麻醉维持,麻醉时间共6h.D组腹腔注射右美托咪定25μg/kg;D+A+S组:腹腔注射右美托咪定25μg/kg、阿替美唑250μg/kg,其余处理同S组.麻醉结束后,每组随机选取12只大鼠处死,收集血液样本,采用ELISA法测定血清皮质酮浓度.每组随机选取24只大鼠于70日龄时行前脉冲抑制实验.计算前脉冲抑制率(PP3%、PP6%、PP12%).80日龄时进行束缚应激实验测定血清皮质酮浓度.结果4组PP6%和PP12%比较差异无统计学意义(P>0.05);与C组比较,S组和D+A+S组PP3%降低,麻醉结束后和80日龄束缚应激实验时血清皮质酮浓度升高(P<0.05),D组上述指标差异无统计学意义(P>0.05);与S组比较,D组PP3%升高,麻醉结束后和80日龄束缚应激实验时血清皮质酮浓度降低(P<0.05),D+A+S组上述指标差异无统计学意义(P>0.05);与D组比较,D+A+S组PP3%降低,麻醉结束后和80日龄束缚应激实验时血清皮质酮浓度升高(P<0.05).结论右美托咪定可减轻新生大鼠七氟醚麻醉后远期感觉运动门控系统损伤,机制可能与激活中枢α2受体,改善下丘脑-垂体-肾上腺皮质轴功能亢进有关.

Objective To evaluate the effect of dexmedetomidine on the long-term sensorimotor gating system after sevoflurane anaesthesia in neonatal rats.Methods One hundred forty-four clean-grade healthy male Sprague-Dawley rats,aged 4-6 days,weighing 8-15 g,were divided into 4 groups(n=36 each)using a random number table method:control group(group C),sevoflurane group(group S),dexmedetomidine plus sevoflurane group(group D+S),and dexmedetomidine plus α2 receptor antagonist atipamezole plus sevoflurane group(group D+A+S).In group S,anesthesia was induced with 6% sevoflurane for 3 min and maintained with 2.1% sevoflurane,and the anesthesia time was 6 h in total.Dexmedetomidine 25μg/kg was intraperitoneally injected in group D.In group D+A+S,dexmedetomidine 25μg/kg and atipamezole 250μg/kg were intraperitoneally injected,and the other treatments were similar to those previously described in group S.Twelve rats in each group were randomly selected after anesthesia and sacrificed,and blood samples were collected for determination of serum corticosterone concentrations by enzyme-linked immunosorbent assay.Twenty-four rats were randomly selected in each group,and prepulse inhibition(PPI)of startle test was performed at 70 days after birth.PPI rate(PP3%,PP6%,PP12%)was calculated.The serum corticosterone concentration was measured by restraint stress test on 80 days after birth.Results There was no significant difference in PP6% or PP12% among the four groups(P>0.05).Compared with group C,PP3%was significantly decreased,and the serum corticosterone concentration was increased after the end of anesthesia and during restraint stress test at 80 days after birth in S and D+A+S groups(P<0.05),and no significant change was found in the parameters mentioned above in group D(P>0.05).Compared with group S,PP3%was significantly increased,and the serum corticosterone concentration was decreased after the end of anesthesia and during restraint stress test at 80 days after birth in group D(P<0.05),and no significant change was found in the parameters mentioned above in group D+A+S(P>0.05).Compared with group D,PP3%was significantly decreased,and the serum corticosterone concentration was increased after the end of anesthesia and during restraint stress test at 80 days after birth in group D+A+S(P<0.05).Conclusion Dexmedetomidine can alleviate the damage to long-term sensorimotor gating system after sevoflurane anesthesia in neonatal rats,and the mechanism may be related to activating centralα2 receptors and improving hypothalamic-pituitary-adrenal axis hyperfunction.