布托啡诺减轻老年大鼠胫骨骨折术后认知功能障碍的作用机制研究  

Action Mechanism of Butorphanol on Cognitive Dysfunction after Tibial Fracture Surgery in Aged Rats

作　　者：杨清龄 赵继波[2] 袁明霞[2] 田乐 高书军 Yang Qingling;Zhao Jibo;Yuan Mingxia;TianLe;Gao Shujun(Department of Anesthesiology,the Second Hospital of/hangjiakou,Hebei Zhangjiakou 075000,China;Department of Anesthesiology,the First Hospital Affiliated to Hebei North College)

机构地区：[1]张家口市第二医院麻醉科,河北张家口075000 [2]河北北方学院附属第一医院麻醉科

出　　处：《中国药师》2021年第8期440-444,共5页China Pharmacist

基　　金：河北省医学科学研究课题计划项目(编号:20201318)。

摘　　要：目的:探讨布托啡诺通过调节大麻素2型受体(CB2R)表达,减轻大鼠胫骨骨折术后认知功能障碍的作用。方法:48只SD雄性大鼠随机分为正常对照组、模型组、布托啡诺低(50μg·kg^(-1))、高(100μg·kg^(-1))剂量组,每组12只。模型组、布托啡诺低、高剂量组大鼠行开放性胫骨骨折手术;布托啡诺低、高剂量组大鼠于术后第1天开始尾静脉注射相应药物(注射体积1 ml/100 g),正常对照组和模型组大鼠尾静脉注射等体积生理盐水,1次/d,连续给药2周,给药周期结束后检测逃避潜伏期、经过原平台位置的次数、原平台象限停留的时间,TUNEL染色观察大鼠海马组织形态学,实时荧光定量PCR和蛋白免疫印迹法测定海马组织CB2R mRNA和蛋白水平;酶联免疫吸附法测定海马组织白细胞介素-2(IL-2)、肿瘤坏死因子-α(TNF-α)水平。结果:正常大鼠海马组织结构正常,神经元排列整齐;模型组大鼠海马组织神经元排列紊乱,可见明显凋亡细胞,炎症细胞浸润;布托啡诺干预后,海马结构趋于正常,神经元凋亡减少,炎症细胞浸润减少。与正常对照组比较,模型组、布托啡诺低、高剂量组大鼠逃避潜伏期、海马组织CB2R mRNA和蛋白水平、IL-2、TNF-α水平升高,经过原平台位置的次数、原平台象限停留的时间降低(P<0.05);与模型组比较,布托啡诺低、高剂量组大鼠逃避潜伏期、海马组织CB2R mRNA和蛋白水平、IL-2、TNF-α水平降低,经过原平台位置的次数、原平台象限停留的时间升高,且两个剂量组间差异有统计学意义(P<0.05)。结论:布托啡诺可改善胫骨骨折术后认知功能障碍大鼠认知缺陷,其机制可能与布托啡诺降低大鼠海马组织CB2R mRNA和蛋白表达进而抑制CB2R通路的激活有关。Objective:To investigate the effects of butorphanol on cognitive dysfunction after tibial fracture surgery in rats by regulating cannabinoid type 2 receptor(CB2 R)expression.Methods:Totally 48 male SD rats were randomly divided into normal control group,model group,butorphanol low(50μg·kg^(-1))and high(100μg·kg^(-1))dose groups with 12 ones in each group.The rats in model group,butorphanol low and high dose groups were performed open tibial fracture.The rats in butorphanol low and high dose groups were injected with corresponding drug via tail vein on the first day after operation(injection volume:1 ml/100 g),and the rats in normal control group and model group were injected with equal volume of normal saline through tail vein,once a day for 2 weeks.At the end of administration cycle,the escape latency,times of passing through the original platform and time of staying in the original platform quadrant were detected.TUNEL staining was used to observe the histomorphology of hippocampus in rats.The levels of CB2 RmRNA and protein in hippocampus were measured by real-time fluorescent reverse transcription and Western blot.The levels of interleukin-2(IL-2)and tumor necrosis factor-α(TNF-α)in hippocampus were measured by enzyme linked immunosorbent assay.Results:In the normal control group,the hippocampal tissue structure was normal,and the neurons were arranged in order;in the model group,the neurons were arranged disorderly with obvious apoptotic cells and inflammatory cell infiltration;after butorphanol intervention,the hippocampal structure tended to be normal,the apoptosis of neurons decreased,and the infiltration of inflammatory cells decreased.Compared with those in the normal control group,the escape latency,CB2 R mRNA and protein levels in hippocampus,IL-2 and TNF-αlevels in the model group,butorphanol low and high dose groups were increased,the times of passing through the original platform and time of staying in the original platform quadrant were decreased(P<0.05).Compared with those in the model gro

关 键 词：布托啡诺 大麻素2型受体 骨折 认知功能障碍 

分 类 号：R965.1[医药卫生—药理学]