针刺通过调控高迁移率族蛋白1/晚期糖基化终末产物受体信号通路对血管性痴呆大鼠认知功能和神经炎症的影响  

The impacts of acupuncture on cognitive function and neuroinflammation in vascular dementia rats by regulating the HMGB1-RAGE signal axis

作　　者：廖晶晶 朱雅琪 何诚 陈丽川[4] LIAO Jingjing;ZHU Yaqi;HE Cheng;CHEN Lichuan(Department of Integrated Medicine/Department of Traditional Chinese Medicine,Tianyou Hospital Affiliated to Wuhan University of Science&Technology,Wuhan,Hubei 430000;Department of Laboratory Medicine,Maternal and Child Health Hospital of Hubei Province,Wuhan,Hubei 430000;Department of Rehabilitation Medicine,the Central Hospital of Wuhan,Wuhan,Hubei 430000;Department of Acupuncture,Wuhan Hospital of Traditional Chinese Medicine,Wuhan,Hubei 430000)

机构地区：[1]武汉科技大学附属天佑医院中西医结合科/中医科,湖北武汉430000 [2]湖北省妇幼保健院检验科,湖北武汉430000 [3]湖北省武汉市中心医院康复医学科,湖北武汉430000 [4]湖北省武汉市中医医院针灸科,湖北武汉430000

出　　处：《河北中医》2024年第12期2010-2016,2023,共8页Hebei Journal of Traditional Chinese Medicine

基　　金：湖北省卫生健康委员会2018~2019年度中医药科研立项项目(编号:ZY2019M053)。

摘　　要：目的探讨针刺对血管性痴呆(VD)大鼠认知障碍、神经炎症及高迁移率族蛋白1(HMGB1)/晚期糖基化终末产物受体(RAGE)信号通路的影响。方法将72只成年雄性SD大鼠分为对照组、模型组、治疗组和抑制剂组,每组18只。除对照组外,其余3组建立VD模型,然后对照组和模型组大鼠予0.9%氯化钠注射液灌胃,治疗组予针刺治疗+0.9%氯化钠注射液灌胃,抑制剂组予甘草酸3 mg/mL灌胃,均每日1次,连续2周。Morris水迷宫试验观察各组大鼠平均逃避潜伏期、游泳总路程、首次抵达平台时间、穿越平台次数;酶联免疫吸附法(ELISA)检测各组大鼠血清肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、IL-10、转化生长因子β(TGF-β)水平;苏木素-伊红(HE)染色观察各组大鼠海马CA1区形态学变化;TUNEL染色观察海马CA1区神经元凋亡;免疫荧光检测海马组织小胶质细胞激活情况;Western blot法检测海马组织B细胞淋巴瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、HMGB1、RAGE蛋白表达水平。结果与对照组相比,模型组大鼠平均逃避潜伏期、游泳总路程、首次抵达平台时间更长(P<0.05),穿越平台次数更少(P<0.05),血清TNF-α、IL-1β水平升高(P<0.05),IL-10、TGF-β水平降低(P<0.05),海马CA1区损伤严重,神经元凋亡率上升(P<0.05),神经元减少,小胶质细胞增多,海马组织小胶质细胞标记物离子钙接头蛋白(IBA-1)、CD68阳性率升高(P<0.05),海马组织Bax、HMGB1、RAGE蛋白表达升高(P<0.05),Bcl-2蛋白表达降低(P<0.05)。与模型组相比,治疗组和抑制剂组平均逃避潜伏期、游泳总路程、首次抵达平台时间缩短(P<0.05),穿越平台次数增多(P<0.05),血清TNF-α、IL-1β水平降低(P<0.05),IL-10、TGF-β水平升高(P<0.05),海马CA1区损伤减轻,神经元增多,小胶质细胞减少,神经元凋亡率、IBA-1、CD68阳性率及Bax、HMGB1、RAGE蛋白表达均降低(P<0.05),Bcl-2蛋白表达升高(P<0.05)。结论针刺可以通过抑制HMGB1/RObjective To investigate the impacts of acupuncture on cognitive function,neuroinflammation and the high mobility group box-1(HMGB1)/receptor for advanced glycation end products(RAGE)signaling pathway in vascular dementia(VD)rats.Methods A total of 72 adult male Sprague-Dawley(SD)rats were randomly divided into the control group,model group,treatment group and inhibitor group,with 18 rats per group,and the VD model was established except rats in the control group.Except for the inhibitor group,oral gavage of 0.9%NaCl solution daily for consecutive 2 weeks was performed in the other groups.Acupuncture was additionally given to rats of treatment group,and oral gavage of glycyrrhizic acid 3 mg/mL once daily was given to rats of inhibitor group for consecutive 2 weeks.Morris water maze test was performed to record the mean escape latency,cumulative distance to the platform,time spent to first reach the platform and number of platform crossings.The enzyme-linked immunosorbent assay(ELISA)was conducted to measure serum tumor necrosis factor alpha(TNF-α),interleukin-1 beta(IL-1β),IL-10 and transforming growth factor beta(TGF-β).The hematoxylin and eosin(HE)staining was applied to observe the morphological changes in the CA1 region of the rat hippocampus.The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)staining was applied to detect neuronal apoptosis in the hippocampal CA1 region.Immunofluorescence was applied to detect the activation of microglia.Western blot was applied to detect the expression levels of B-cell lymphoma factor 2(Bcl-2),Bcl-2 associated X protein(Bax),HMGB1,and RAGE.Results Compared with those of the control group,rats in the model had significantly longer mean escape latency,cumulative distance to the platform and time spent to first reach the platform,less number of platform crossings,higher serum TNF-αand IL-1β,lower serum IL-10 and TGF-β,severer damage in the hippocampal CA1 region,higher apoptotic rate in neurons,less number of neurons,greater number of microgl

关 键 词：痴呆 血管性 大鼠 针灸 高迁移率族蛋白质类 高级糖化终产物受体 认知障碍 动物实验 

分 类 号：R245.111[医药卫生—针灸推拿学]