老年小鼠伏隔核多巴胺D1受体表达下调参与异氟醚麻醉后苏醒延迟

Downregulation of dopamine D1 receptor expression in the nucleus accumbens of aged mice is involved in the delayed recovery after isoflurane anesthesia

目的探讨伏隔核中多巴胺D1受体的老年化改变在老年小鼠异氟醚麻醉后苏醒延迟中的作用。方法老年(18~22月龄)和青年(5~8月龄)小鼠各26只,每组采用随机数字表法抽取8只,经1.4%异氟醚麻醉后,比较2组小鼠异氟醚麻醉后苏醒时间及脑电频谱的差异。剩余小鼠建立老年和青年伏隔核微注射模型,比较微注射多巴胺D1受体激动剂、拮抗剂以及生理盐水对老年和青年小鼠异氟醚麻醉苏醒时间及苏醒期脑电频谱的影响;最后通过Western blot检测老年和青年伏隔核内多巴胺D1受体的表达水平的差异,分析老年小鼠麻醉后苏醒延迟的可能机制。结果与青年小鼠相比,老年小鼠异氟醚麻醉后苏醒时间明显延长(P<0.01),同时皮层脑电图(EEG)频谱中δ频段(>1~4 Hz)能量明显升高(P<0.01),而α(>8~12 Hz)、β(>12~25 Hz)和γ(>25~60 Hz)频段的能量显著降低(均P<0.05)。与注射生理盐水组相比,在伏隔核中微注射D1受体激动剂明显缩短了青年小鼠苏醒时间,同时EEG上显示δ频段能量减少,γ频段能量增加(P<0.01);注射D1受体拮抗剂则显著延长了青年小鼠的苏醒时间,增加了δ频段能量(P<0.01)。然而,注射D1受体激动剂/拮抗剂对老年小鼠的苏醒时间与皮层EEG均无显著影响(P>0.05)。Western blot结果显示,老年小鼠伏隔核中多巴胺D1受体表达水平较青年小鼠显著降低(P<0.01)。结论老年小鼠伏隔核D1受体表达的下调减弱了其促全身麻醉觉醒的作用,可能是老年动物麻醉后苏醒延迟的重要原因之一。

Objective To explore the role of the age-related alteration of dopamine D1 receptor in nucleus accumbens(NAc)in the delayed emergence from isoflurane anesthesia in aged mice.Methods Firstly 8 aged mice(18-22 months)and 8 young mice(5-8 months)were extracted from 26 mice in each group.After exposure to 1.4%isoflurane,differences in the emergence time from isoflurane anesthesia and power spectrum of cortical electroencephalogram(EEG)were compared between the two groups.The rest of the mice in each group were used for microinjection.The effect of microinjecting dopamine D1 receptor agonist,antagonist and normal saline into the NAc on the emergence time and power spectrum were investigated during the recovery period after isoflurane anesthesia.Finally,the differences of expression levels of the NAc dopamine D1 receptor in aged and young mice were detected to analyze the potential mechanism underlying the delayed emergence after general anesthesia in aged mice.Results Compared with young mice,the emergence time from isoflurane anesthesia was notably prolonged in aged mice(P<0.01).Power ofδband(>1-4 Hz)in the cortical EEG was elevated in aged mice(P<0.01),whilst the power ofαband(>8-12 Hz),βband(>12-25 Hz)andγband(>25-60 Hz)were strikingly reduced(P<0.05).Comparing with normal saline controls,microinjecting D1 receptor agonist significantly shortened the emergence time,reduced the power ofδband and enhanced the power ofγband in EEG of young mice(P<0.01).Meanwhile,microinjecting D1 receptor antagonist prolonged the emergence time and increased the power inδband in young mice(P<0.01).However,microinjecting D1 receptor agonist/antagonist affected neither the emergence time nor cortical EEG in aged mice(P>0.05).In addition,the expression level of D1 receptor in the NAc remarkably decreased in aged mice compared with that of young mice(P<0.01).Conclusion The age-related downregulation of D1 receptor in the NAc attenuates its arousal-promoting ability for general anesthesia,which is probably a crucial reason for the delayed emergence in aged animals.