Orexin-A对氯胺酮麻醉老年大鼠学习记忆及基底前脑ChAT表达的影响

Effect of orexin-A on learning-memory ability and ChAT expression in basal forebrain of aged rats after ketamine anesthesia

目的观察orexin-A对氯胺酮麻醉老年大鼠学习记忆及基底前脑ChAT表达的影响,并探讨其可能机制。方法将40只老年大鼠,随机分为空白对照组、模型对照组、orexin-A低剂量组、orexin-A高剂量组,各10只。以100 mg/kg氯胺酮腹腔注射建立实验模型。麻醉10 min后,治疗组侧脑室注入orexin-A 1、4nmol/10μL。对照组注入等量人工脑脊液。以Morris水迷宫行为学及免疫组化方法,观察麻醉后大鼠学习记忆功能和基底前脑胆碱乙酰基转移酶(ChAT)的表达变化。结果(1)氯胺酮麻醉后老年大鼠Morris水迷宫成绩明显下降,orexin-A可提高水迷宫各观察指标成绩,以4nmol剂量效果显著(P<0.05,P<0.01)。(2)氯胺酮麻醉后,基底前脑ChAT表达降低,4nmol orexin-A能部分逆转其变化(P<0.05)。结论一定剂量orexin-A可明显改善氯胺酮麻醉后老年大鼠学习记忆功能。此效应可能与其逆转麻醉后大鼠基底前脑ChAT的低表达密切相关。

Objective To observe the effect of orexin-A on learning-memory ability and ChAT expressions in basal forebrain of aged rats after ketamine anesthesia and to explore the mechanism of orexin-A on the cognitive function after anesthesia. Methods Forty aged rats were divided randomly into 4 groups：control group, model control group, orexiwA l nmol group; orexin A 4nmol group. All model groups received an intraperitoneal injection of ketamine at 100mg/kg. Control group got normal saline at the same dose only. 10min after injection, the groups received an intracerebroventricular injection of ASCF（eontrol and model control group）, orexin A l nmol,orexiwA 4nmol at 10μL, respectively. The Morris water maze was used to test the ability of learning and spatial lo calization on rats. Immunocytochemistry was used to evaluate the effect of orexin-A on choline acetyltransferases in basal forebrain. Results （1）Ketamine impaired the ability of learning and memory on aged rats. Orexin-A at dose of 4nmol can improve the ability of learning and spatial localization on aged rats after anesthesia（P〈0.05 ,P〈0.01）. （2）The expression of ChAT in basal forebrain of aged rat decreased after ketamine anesthesia. Orexin A at dose of 4nmol acted as a protective factor and increased the expression of ChAT in basal forebrain significantly（P〈0.05）. Conclusion When ketamine is administered in aged rats,it can affect the spatial learning and memory behavior. The mechanism of damage might be related to the central cholinergic system. A high dose of orexiw A could partly reverse this change.