α7 烟碱型乙酰胆碱受体在右美托咪定及褪黑素协同防治大鼠谵妄中的作用

摘要

目的 探讨右美托咪定及褪黑素协同防治大鼠谵妄的作用及右美托咪定及褪黑素对α7 烟碱型乙酰胆碱受体(α7AchR)的调节作用.方法 雄性 SD大鼠 30 只,6~8 周龄,随机分为六组:对照组(C组)、东莨菪碱诱导谵妄模型组(S组)、右美托咪定组(D组)、褪黑素组(M组)、α-银环蛇毒素(α-BGT)拮抗组(BM组)和右美托咪定+褪黑素组(DM组),每组 5 只.S组腹腔注射 0.5 %东莨菪碱 1.8 mg/kg建立谵妄大鼠模型;C组用等容量生理盐水代替建模药物;D 组及 DM组于建模前1 5 min腹腔注射右美托咪定40 μg/kg;BM组于建模前1 5 min腹腔注射α-BGT 1 μg/kg;M组、BM组及DM组建模后立即在对侧腹腔注射褪黑素 5 mg/kg.分别于造模前 1 5 min 及造模后 1 0 min进行旷场实验.实验结束后处死大鼠,经内眦取血,采用 ELISA 法检测大鼠血清α7nAchR 浓度.结果 与C组比较,S组周围格路程、旷场总路程明显延长,周围格速度、旷场总速度明显加快(P<0.05);与S组比较,D组、M组、DM组周围格路程、旷场总路程明显缩短,周围格速度、旷场总速度明显减慢(P<0.0 1 ).与D组比较,DM组周围格路程、旷场总路程明显缩短(P<0.05).与 C组比较,S组α7nAChR浓度明显降低(P<0.05);与 S 组比较,D 组α7nAChR 浓度明显升高(P<0.0 1 ).结论 右美托咪定可改善谵妄症状,可能是通过提高α7nAChR 表达.而褪黑素可能增强右美托咪定的谵妄防治效果.%Objective To observe dexmedetomidine coordinate with mlelatonin attenuate the scopolamine-induced delirium in rats and its mechanism.Methods Thirty male adult SD rats aged 6-8 weeks were randomly divided into six groups:normal saline control group (group C),scopolamine-induced delirious model group (group S),dexmedetomidine group (group D),mlelaton group (group M),α-bungarotoxin antagonism group (group BM),joint protection group (group DM).A model of delirium was reproduced by intraperitoneal inj ection of scopolamine 1.8 mg/kg.The rats in group C was given equal sterile normal saline instead,the rats in group D was intraperitoneal injected of dexmedetomidine 40 μg/kg 15 minutes before scopolamine injection,the rats in group M was intrap-eritoneal injected of mlelaton 5 mg/kg in the contralateral abdominal at the same time with scopolamine injection,the rats in group BM was intraperitoneal injected ofα-BGT 1 μg/kg 15 minutes before scopolamine injection and mlelaton 5 mg/kg in the contralateral abdominal at the same time with scopolamine injection,the rats in group DM was intraperitoneal injected of dexmedetomidine 40 μg/kg 15 minutes before scopolamine injection and mlelaton 5 mg/kg in the contralateral abdominal at the same time with scopolamine injection.The rats were assigned for open field test 15 minutes before and 10 minutes after model reproduction for 15 minutes.The level ofα7nAchR in serum was deter-mined by enzyme linked immunosorbent assay.Results When compared with group C,rats in group S ran significant longer total distance and space distance,had faster total speed and space speed (P<0.05).When compared with group S,rats in group D,group M,group DM ran significant shorter total distance and space distance,had significant slower total speed and space speed (P<0.01 );when compared with group D,rats in group DM ran significant shorter total distance and space dis- tance (P<0.05 ),had slower total speed and space speed,however without significant statistical difference.When compared with that in group C,the level of α7nAChR in serum were significantly decreased in group S (P<0.05).When compared with group S,the level of α7nAChR were signifi-cantly increased in group D (P<0.01).There were no significant difference between group M and group S (P=0.96).When compared with group D,the level of α7nAChR had an elevated trend in group DM.Conclusion Dexmedetomidine can improve the symptoms of delirium,possibly by in-creasing the activity of alpha 7nAChR.Melatonin may improve the effect of dextromidine on delirium.