电针预处理对老龄大鼠长期术后认知功能障碍和神经炎性反应的影响  

Effects of electroacupuncture pretreatment on long-term postoperative cognitive dysfunction and neuron-inflammation in aged rats

作　　者：王志刚 刘真富[3] 高扬 陈永学 尹春平 王秋筠 WANG Zhi-gang;LIU Zhen-fu;GAO Yang;CHEN Yong-xue;YIN Chun-ping;WANG Qiu-jun(Department of Ane sthesiology,Handan Central Hospital Affiliated to Hebei Medical University,Handan 056008,Hebei Province,China;Department of Day Surgery,The Third Affiliated Hospital of Hebei Medical University,Shijiazhuang 05005l;Department of Anesthesiology,Zaozhuang Hospital,Zaozhuang 27710l,Shandong Province)

机构地区：[1]河北医科大学附属邯郸市中心医院麻醉科,河北邯郸056008 [2]河北医科大学附属第三医院日间手术部,石家庄050051 [3]枣庄医院麻醉科,山东枣庄277101

出　　处：《针刺研究》2023年第6期557-563,共7页Acupuncture Research

基　　金：国家自然科学基金项目(No.81771134)。

摘　　要：目的:观察电针预处理对老龄大鼠术后认知功能障碍、神经元凋亡及神经炎性反应的影响。方法:20月龄雄性SD大鼠随机分为假手术组、模型组、电针组,每组12只。采用胫骨骨折内固定术制备术后认知功能障碍老龄大鼠模型。电针组在进行左侧胫骨骨折手术前5d选取大鼠右侧“足三里”“合谷”“内关”进行电针刺激,疏密波2Hz/15Hz,30min/次,1次/d,连续5d。术后31—35d采用Morris水迷宫实验评价大鼠认知功能,采用Tunel/NeuN双染法观察海马神经元凋亡情况,免疫荧光染色法检测海马齿状回小胶质细胞高迁移率族蛋白B1(HMGB1)、磷酸化(p)-核因子(NF)-κB阳性表达,Westernblot法检测海马组织中白细胞介素(IL)-6和IL-1β蛋白表达水平。结果:与假手术组比较,模型组大鼠逃避潜伏期明显延长(P<0.05),跨越原平台次数、目标象限游泳路程和时间占比显著降低(P<0.05);海马神经元凋亡率明显升高(P<0.05);海马齿状回小胶质细胞HMGB1和p-NF-κB免疫荧光表达明显升高(P<0.05);海马组织中IL-6和IL-1β蛋白表达水平升高(P<0.05)。与模型组比较,电针组大鼠逃避潜伏期明显缩短(P<0.05),跨越原平台次数、目标象限游泳路程和时间占比明显升高(P<0.05);海马神经元凋亡率明显降低(P<0.05);海马齿状回小胶质细胞HMGB1和p-NF-κB免疫荧光表达明显降低(P<0.05);海马组织中IL-6和IL-1β蛋白表达水平降低(P<0.05)。结论:电针预处理可改善胫骨骨折内固定术后认知功能障碍老龄大鼠的海马神经炎性反应,降低神经元凋亡率,改善术后长期认知功能障碍,其机制可能与抑制海马齿状回小胶质细胞HMGB1/NF-κB通路有关。Objective To observe the effects of electroacupuncture pretreatment on postoperative cognitive dysfunction(POCD),neuronal apoptosis and neuron-inflammation in aged rats.Method Thirty-six male SD rats aged 20 months were randomly divided into sham operation group,model group and electroacupuncture(EA)group,with 12 rats in each group.The POCD rats model was prepared by internal fixation of left tibial fracture.Five days before modeling,EA stimulation(2 Hz/15 Hz,1 mA,30 min)was applied to“Zusanli”(ST36),“Hegu”(LI4)and“Neiguan”(PC6)on the unaffected side of rats in the EA group,once a day for consecutive 5 d.The learning and memory abilities of rats were evaluated by water maze test 31—35 days after operation.The apoptosis of hippocampal neurons was observed by Tunel/NeuN double staining.The expressions of high mobility group protein B1(HMGB1)and phosphorylated(p)-nuclear factor(NF)-κB in microglia cells in hippocampal dentate gyrus were detected by immunofluorescence staining.The expression levels of interleukin(IL)-6 and IL-1βin the hippocampus were detected by Western blot.Results Compared with the sham operation group,the escape latency was prolonged(P<0.05);the frequency of crossing the original platform,ratio of the swimming distance and the time in the target quadrant of the Morris water maze were significantly decreased(P<0.05);the apoptosis rate of hippocampal neurons was significantly increased(P<0.05);the expressions of HMGB1 and p-NF-κB in microglia cells in the dentate gyrus and the expression levels of IL-6 and IL-1βin hippocampus were increased(P<0.05)in the model group.Compared with the model group,the results of the above indexes were all opposite(P<0.05)in the EA group.Conclusion EA preconditioning can regulate hippocampal inflammatory response,alleviate neuronal apoptosis rate and long-term cognitive dysfunction in aged rats with POCD,the mechanisms may be related to the inhibition of microglia HMGB1/NF-κB pathway in hippocampal dentate gyrus.

关 键 词：电针 神经炎性反应 术后认知功能障碍 高迁移率族蛋白B1 

分 类 号：R245.97[医药卫生—针灸推拿学]