右美托咪定对新生大鼠七氟醚麻醉后远期焦虑状态的影响:中枢不同亚型α2受体在其中的作用

摘要

Objective To evaluate the effect of dexmedetomidine on the long-term anxiety state after sevoflurane anesthesia in neonatal rats and the role of different central subtypes of α2 receptors.Methods A total of 216 clean-grade healthy male Sprague-Dawley rats,aged 4-6 days,weighing 8-15 g,were divided into 6 groups (n =36 each) using a random number table method:control group (group C),sevoflurane group (group S),dexmedetomidine + sevoflurane group (group D+S),dexmedetomidine + α2 receptor antagonist atipamezole + sevoflurane group (group D+A+S),dexmedetomidine + α2A receptor antagonist BRL44408 + sevoflurane group (group D+B+S),and dexmedetomidine + α2C receptor antagonist JP1302 + sevoflurane group (group D+J+S).Anesthesia was induced by inhaling 6％ sevoflurane for 3 min and maintained by inhaling 2.1％ sevoflurane for 6 h.At 30 min before anesthesia induction,dexmedetomidine 25 μg/kg was intraperitoneally injected in group D+S,dexmedetomidine 25 μg/kg and atipamezole 250 μg/kg were intraperitoneally injected in group D + A + S,dexmedetomidine and α2A receptor antagonist BRL44408 1.5 mg/kg were intraperitoneally injected in group D+B+S,and dexmedetomidine 25 μg/kg and α2C receptor antagonist JP1302 3 mg/kgwere intraperitoneally injected in group D+J+S.Twelve rats in each group were randomly selected and sacrificed after the end of anesthesia,blood samples were collected for blood gas analysis,and the serum corticosterone concentration was measured by enzyme-linked immunosorbent assay.The elevated plus maze was performed when the left rats in each group were 60 days old,and 12 rats were selected when the they were 80 days old to perform the restraint stress test.Results Compared with group C,the percentage of time of staying at the open arm was significantly decreased,the total motion distance was shortened,and the serum corticosterone concentration was increased after the end of anesthesia and during the restraint stress test in S,D+A+S and D+B+S groups (P＜0.05),and no significant change was found in the parameters mentioned above in D+S and D+J+S groups (P＞0.05).Compared with group S,the percentage of time of staying at the open arm was significantly increased,the total motion distance was prolonged,and the serum corticosterone concentration was decreased after the end of anesthesia and during the restraint stress test in group D+S and group D+J+S (P＜0.05),and no significant change was found in the parameters mentioned above in group D+A+S and group D+B+S (P ＞0.05).Compared with group D+S,the percentage of time of staying at the open arm was significantly decreased,the total motion distance was shortened,and the serum corticosterone concentration was increased after the end of anesthesia and during the restraint stress test in D+A+S and D+B+S groups (P＜0.05),and no significant change was found in the parameters mentioned above in group D+J +S (P＞ 0.05).Conclusion Dexmedetomidine can reduce the long-term anxiety state after sevoflurane anesthesia in neonatal rats,and the mechanism may be related to activating central α2A receptors and improving hypothalamic-pituitary-adrenocortical axis hyperfunction.%目的 评价右美托咪定对新生大鼠七氟醚麻醉后远期焦虑状态的影响及中枢不同亚型α2受体在其中的作用.方法 清洁健康雄性SD大鼠216只,4～6日龄,体重8～15g,采用随机数字表法分为6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)、右美托咪定+α2受体拮抗剂阿替美唑+七氟醚组(D+A+S组)、右美托咪定+α2A受体拮抗剂BRL44408+七氟醚组(D+B+S组)和右美托咪定+α2C受体拮抗剂JP1302+七氟醚组(D+J+S组).七氟醚麻醉方法:吸入6％七氟醚麻醉诱导3 min,2.1％七氟醚麻醉维持6h.麻醉诱导前30 min,D+S组腹腔注射右美托咪定25 μg/kg,D+A+S组腹腔注射右美托咪定25μg/kg和阿替美唑250 μg/kg,D+B+S组腹腔注射右美托咪定25 μg/kg和α2A受体拮抗剂BRL44408 1.5 mg/kg,D+J+S组腹腔注射右美托咪定25 μg/kg和α2C受体拮抗剂JP1302 3 mg/kg.麻醉结束后,随机选取12只大鼠处死,收集血样,进行血气分析,并采用ELISA法测定血清皮质酮浓度.剩余大鼠在60日龄时进行高架十字迷宫实验,80日龄时随机选取12只大鼠,进行束缚应激实验.结果 与C组比较,S组、D+A+S组和D+B+S组开放臂停留时间百分比降低,总运动距离缩短,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+S组和D+J+S组上述指标差异无统计学意义(P＞0.05);与S组比较,D+S组和D+J+S组开放臂停留时间百分比升高,总运动距离延长,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组和D+B+S组上述指标差异无统计学意义(P＞0.05);与D+S组比较,D+A+S组和D+B+S组开放臂停留时间百分比降低,总运动距离缩短,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+J+S组上述指标差异无统计学意义(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焦虑状态,机制可能与激活中枢α2A受体,改善下丘脑-垂体-肾上腺皮质轴功能亢进有关.