逐增剂量法和稳定剂量法腹腔注射羟考酮的老年大鼠认知功能障碍对比观察  

Observation of cognitive dysfunction in elderly rats intraperitoneally injected with oxycodone by increasing-dose method versus stable-dose method

作　　者：高婧 袁静静[1] 徐玉灿[1] GAO Jing;YUAN Jingjing;XU Yucan(Department of Anesthesiology and Perioperative Medicine,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院麻醉与围术期医学部,郑州450052

出　　处：《山东医药》2021年第36期41-44,共4页Shandong Medical Journal

基　　金：国家卫生健康委科学研究基金河南省医学科技攻关计划省部共建重点项目(SBGJ202002066)。

摘　　要：目的比较分别采用逐增剂量法和稳定剂量法腹腔注射羟考酮的老年大鼠认知功能障碍情况。方法选取清洁级20月龄雄性SD大鼠30只,随机分为3组各10只。A组大鼠腹腔注射羟考酮,剂量为0.2 mg/(kg·d),1次/d,连续14 d;B组大鼠腹腔注射羟考酮,剂量从0.1 mg/(kg·d)递增至0.7 mg/(kg·d),每日递增剂量0.1 mg/kg,1次/d,连续7 d;C组大鼠腹注射生理盐水,2 mL/d,1次/d,连续7 d。给药或生理盐水结束后开始进行水迷宫游泳训练和测试,训练为期3 d。训练后进行定位航行实验(PNT),为期3天(PNT 1~3)。PNT后取出水中平台进行空间探索实验(SPT)。SPT后1周,放回平台再次进行PNT(PNT4)。结果与C组比较,B组大鼠PNT2、PNT4平台逃避潜伏期长和穿越平台次数少,A组PNT4平台逃避潜伏期长、穿越平台次数少(P均<0.05);与B组比较,A组PNT4平台逃避潜伏期短、穿越平台次数多(P均<0.05)。结论长期使用羟考酮可能引起大鼠认知功能障碍,稳定剂量法较逐增剂量法对学习、记忆功能损害较小,且停药以后认知功能障碍可较快恢复;逐增剂量方案对学习和记忆功能均有较大的损害,短期恢复差。Objective To observe the cognitive dysfunction of elderly rats intraperitoneally injected with oxycodone by increasing-dose method versus stable-dose method.Methods Thirty clean-grade male Sprague-Dawley rats aged20 months were selected and randomly divided into 3 groups with 10 rats in each.Rats in the group A were injected intraperitoneally with oxycodone at a dose of 0.2 mg/(kg·d)once per day for 14 consecutive days.Rats in the group B were injected intraperitoneally for 7 consecutive days,once a day,the dose increased from 0.1 mg/(kg·d)to 0.7 mg/(kg·d),and the daily increased dose was 0.1 mg/Kg.Rats in the group C were intraperitoneally injected with normal saline 2 mL/d,once a day for 7 consecutive days.After the administration or normal saline,the training and testing of water maze swimming started,and the training lasted for 3 days.After training,we carried out the place navigation test(PNT)for 3 days(PNT1-3).After PNT,the underwater platform was taken out for space probe test(SPT).At 1 week after SPT,we put the rats back on the platform and perform PNT again(PNT4).Results Compared with group C,rats in the group B had longer platform escape latency and fewer platform crossing times on PNT2 and PNT4,and rats in the group A had longer platform escape latency and fewer platform crossing times on PNT4(all P<0.05).Compared with group B,rats in the group A had a short platform escape latency and more platform crossing times on PNT4(both P<0.05).Conclusions Long-term use of oxycodone may cause cognitive dysfunction in rats.The stable dose method has less damage to learning and memory function than the incremental dose method,and the cognitive dysfunction can be recovered more quickly after the drug is stopped.The incremental dose method has great damage to the learning and memory functions of rats,and the short-term recovery is poor.

关 键 词：羟考酮 认知功能障碍 空间学习能力 空间记忆能力 

分 类 号：R441.1[医药卫生—诊断学]