海马Chrnb4在老龄小鼠术后谵妄中的作用  

Role of hippocampal Chrnb4 in postoperative delirium in aged mice

作　　者：彭姮玥 李靓静 张明明[1] 何晓帆[1] 王臻[1] 赵晓春[1] Peng Hengyue;Li Liangjing;Zhang Mingming;He Xiaofan;Wang Zhen;Zhao Xiaochun(Department of Anesthesiology,Stomatology Hospital Affiliated to China Medical University,Shenyang 110002,China)

机构地区：[1]中国医科大学附属口腔医院麻醉科,沈阳110002

出　　处：《中华麻醉学杂志》2024年第6期682-687,共6页Chinese Journal of Anesthesiology

摘　　要：目的:评价海马含β4亚基的烟碱型乙酰胆碱受体(Chrnb4)在老龄小鼠术后谵妄中的作用。方法:SPF级雄性C56BL/6J小鼠48只,18月龄,体质量29~35 g。采用随机数字表法分为6组:胫骨骨折手术组(TF组, n=6)、假手术组(Sham组, n=6)、胫骨骨折手术+阿地芬宁组(TA组, n=9)、胫骨骨折手术+对照溶剂组(TV组, n=9)、假手术+阿地芬宁组(SA组, n=9)和假手术+对照溶剂组(SV组, n=9)。采用七氟烷麻醉下胫骨骨折手术制备术后谵妄模型。假手术为仅进行麻醉和皮肤切口并缝合。TA组、TV组、SA组、SV组于术前5 d置入脑室微量给药套管,每组再随机选取3只小鼠,置入海马CA1区微丝阵列电极。于术后30 min时,TA组和SA组脑室输注阿地芬宁(62.5 nmol/μl)2 μl,TV组和SV组给予对照溶剂2 μl,间断24 h给药,连续给予7 d。TF组及Sham组于术后24 h时,采用实时定量PCR法检测海马组织Chrnb4 mRNA表达水平。TA组、TV组、SA组、SV组分别于术后第7、8天采用旷场实验及O迷宫实验评价冲动样行为;行为学实验结束后,采用免疫荧光染色法检测海马CA1区胶质纤维酸性蛋白(GFAP)及囊泡谷氨酸转运蛋白1(Vglut1)的表达,旷场实验期间记录小鼠海马CA1区局部场电位。 结果:与Sham组相比,TF组海马Chrnb4 mRNA表达上调( P<0.05);与TV组相比,TA组和SV组旷场实验中心路程百分比和O迷宫开放象限停留时间百分比降低,CA1区场电位β波功率降低,海马CA1区GFAP和Vglut1表达下调,GFAP +-Vglut1 +共染面积减少( P<0.05)。SA与SV组各指标比较差异无统计学意义( P>0.05)。 结论:海马Chrnb4可能参与了老龄小鼠术后谵妄的发生机制,该过程可能与抑制神经元兴奋性毒性有关。Objective To evaluate the role of hippocampalβ4-Subunit-Containing Nicotinic Acetylcholine Receptors(Chrnb4)in postoperative delirium in aged mice.Methods Forty-eight SPF male C57BL/6J mice,aged 18 months,weighing 29-35 g,were assigned into 6 groups using a random number table method:tibial fracture group(TF group,n=6),sham operation group(Sham group,n=6),tibial fracture+adipenine group(TA group,n=9),tibial fracture+control vehicle group(TV group,n=9),sham operation+adipenine group(SA group,n=9),and sham operation+control vehicle group(SV group,n=9).The postoperative delirium model was prepared by tibial fracture under sevoflurane anesthesia.Tibial fracture was simulated by implanting a steel pin into the tibia and then clamping it,while sham group only received a longitudinal incision and suture after anesthesia.A microinjection cannula was implanted into the mouse skull at 5 days before developing the model in TA group,TV group,SA group and SV group.Three mice from each group were randomly selected for microelectrode implantation in the hippocampal CA1 area.Starting from 30 min after surgery,adipenine(62.5 nmol/μl)2μl was infused into the cerebral ventricle for 7 consecutive days in TA and SA groups,and vehicle(2μl)was administered instead at a 24-h interval for 7 consecutive days in TV and SV groups.The expression of Chrnb4 mRNA in the hippocampal tissues was detected by real-time quantitative polymerase chain reaction at 24 h after surgery.On the 7th and 8th days after surgery,the open-field test and O-maze experiment were conducted to assess the impulsive-like behavior in TA,TV,SA and SV groups.After the behavioral test,the expression of glial fibrillary acidic protein(GFAP)and vesicular glutamate transporter 1(Vglut1)in the hippocampal CA1 region was detected by immunofluorescence staining.The local field potentials in the hippocampal CA1 region were recorded during the open field test.Results The expression of Chrnb4 mRNA in the hippocampal tissues was significantly up-regulated in TF group compared to

关 键 词：谵妄 术后认知并发症 老年人 受体 烟碱 

分 类 号：R614[医药卫生—麻醉学]