Orexin-1受体参与调节老年大鼠异氟醚麻醉苏醒延迟

Orexin-1 Receptor is Involved in Delayed Emergence of Aged Rats from Isofluran Anaesthesia

目的:探索orexin能神经系统是否参与调节老年大鼠异氟醚麻醉觉醒延迟及其具体机制。方法:选择雄性SD大鼠,将其分为老年大鼠组(n=6,20月龄,体重600~800g)和青年大鼠组(n=6,3~4月龄,体重230~250 g)。采用翻正反射恢复时间作为麻醉觉醒时间,记录异氟醚麻醉下老年大鼠和青年大鼠各自的麻醉觉醒时间;通过免疫荧光染色和细胞计数确定老年大鼠和青年大鼠神经元数目,放射免疫法检测两组大鼠血浆orexin-A含量;Western blot检测老年大鼠和青年大鼠orexin-1和-2受体含量。结果:老年大鼠异氟醚麻醉觉醒时间明显长于青年大鼠(P<0.05);老年大鼠orexin能神经元的数目与青年大鼠相比差异无统计学意义(P>0.05),但其血浆orexin-A含量显著高于青年大鼠(P<0.05);老年大鼠orexin-1受体在蛋白质表达中明显低于青年大鼠(P<0.05),而orexin-2受体的表达与青年大鼠相比差异无统计学意义(P>0.05)。结论:在老龄化过程中,虽然血浆中orexin-A含量代偿性增加,但是由于全脑中orexin-1受体含量的减少,使其并不能充分发挥促觉醒作用,这可能是导致老年人麻醉苏醒延迟的原因之一。

Objective:To evaluate whether the orexinergic neurons was involoved in the delayed emergence of aged rats from isoflurane anesthesia.Methods:Male SD rats were selectd and divided into the aged group(n=6,twenty month,weighed 600~800 g)and the young group(n=6,three^four month,weighed 230~250 g).The return of righting reflex from isoflurane anesthesia was recorded as emergence time;the immunofluorescence and cell count were used to detect the number of orexinergic neurons,at the same time,the concentrations of orexin-A in plasma was detected by radioimmunoassay respectively;the expression of orexin-1 receptor and the orexin-2 were analyzed via western blot.Results:The emergence time of aged rats was longer than that of young adult ones in isoflurane anaesthesia(P<0.05).The number of orexinergic neurons showed no statistical difference between the aged and young groups(P>0.05),but the plasmic orexin-A levels were higher in the aged group than that in the young adult group(P<0.05).Otherwise,the expression of orexin-1 receptor of aged group was lower than that in the young group(P<0.05),but the expression of orexin-2 receptor showed no statistical difference compared with that of the young group(P>0.05).Conclusion:Although the content of orexin-A in plasma increases compensatively in the process of aging,the decreased expression of orexin-1 receptor in the whole brain makes it be unable to exert the arousal role,which may be one of the reasons leading to delayed recovery of anesthesia in the elderly from isoflurane anaesthesia.