基于NF-κB/NLRP3/Caspase-1信号通路探讨电针改善阿尔茨海默病模型大鼠认知功能障碍的机制  

Exploring the mechanism of electroacupuncture to improve cognitiveimpairment in alzheimer′s disease model rats based on NF⁃κB/NLRP3/Caspase⁃1 signaling pathway

作　　者：李荣鑫 黄丽 曾悦阳 张淑慧[1] 陈怡然 刘玉丽[1] 马铁明[1] LI Rongxin;HUANG Li;ZENG Yueyang;ZHANG Shuhui;CHEN Yiran;LIU Yuli;MA Tieming(College of Acupuncture and Massage,Liaoning University of Traditional Chinese Medicine,Shenyang 110000,Liaoning,China)

机构地区：[1]辽宁中医药大学针灸推拿学院,辽宁沈阳110000

出　　处：《实用医学杂志》2025年第3期322-329,共8页The Journal of Practical Medicine

基　　金：国家自然科学基金项目(编号:82305391);辽宁省科学技术厅联合基金项目博士科研启动项目(编号:2023-BSBA-221);辽宁省“兴辽英才计划”项目科技创新领军人才项目(编号:XLYC1902004);辽宁省针灸养生康复重点实验室资助项目(编号:18-006-0-06)。

摘　　要：目的观察电针百会、脾俞、足三里对Aβ1-42所致阿尔茨海默病(AD)大鼠学习记忆功能的影响,并从NF-κB/NLRP3/Caspase-1信号通路介导的炎症级联反应探讨电针治疗AD的作用机制。方法采用双侧海马C1区注射Aβ1-42溶液制备AD大鼠模型。按随机数字表法将32只SPF级雄性大鼠分为4组,假手术组、模型组、电针组、西药组(盐酸多奈哌齐),每组8只。电针组予“百会”、“脾俞”和“足三里”穴位电针刺激,西药组予药物灌胃治疗。治疗结束后Morris水迷宫实验检测学习记忆能力;用HE染色观察海马组织形态变化;用ELISA测定血清TNF-α、IL-1β含量;用Western blot和免疫荧光染色分别检测海马区NF-κB p65、NLRP3及Caspase-1的蛋白和荧光双标共表达水平。结果与假手术组比较,造模后模型组大鼠逃避潜伏期明显延长(P<0.05),穿越原平台次数减少,目标象限停留时间减少(P<0.05);细胞核形态改变,海马周围神经元出现坏死、空泡变性,染色质边集;血清TNF-α、IL-1β含量升高(P<0.05);大鼠海马区NF-κB p65、NLRP3、Caspase-1蛋白表达水平和荧光阳性表达升高(P<0.05)。与模型组比较,电针组和西药组大鼠逃避潜伏期有缩短趋势(P<0.05),穿越原平台次数和目标象限停留时间增加(P<0.05),细胞结构基本完整,少许细胞核轻度不规则,染色质部分边集;血清TNF-α、IL-1β含量降低(P<0.05);海马区NF-κB p65、NLRP3、Caspase-1蛋白表达水平和荧光阳性表达降低(P<0.05)。结论电针提高AD大鼠学习记忆能力,可能是通过下调NF-κB/NLRP3/Caspase-1信号通路,减少神经炎性因子的释放,从而改善AD大鼠认知功能障碍。Objective To investigate the effects of electroacupuncture(EA)at“Baihui(GV 20),”“Pishu(BL 20),”and“Zusanli(ST 36)”on the learning and memory functions of rats with Alzheimer′s disease(AD)induced by Aβ1‑42.Additionally,the mechanism of EA in treating AD was explored from the perspective of the inflammatory cascade mediated by the NF‑κB/NLRP3/Caspase‑1 signaling pathway.Methods A rat model of Alzheimer′s disease was established by bilateral injection of Aβ1‑42 solution into the C1 region of the hippocampus.According to the random number table method,32 male SPF‑grade rats were divided into four groups(n=8 per group):a sham‑operated group,a model group,an electroacupuncture(EA)group,and a Western medicine group(donepezil hydrochloride).The EA group received electroacupuncture at the“Baihui”,“Pishu”,and“Zusanli”acupoints;the Western medicine group received donepezil hydrochloride via gavage.After the treatment period,Morris water maze experiments were conducted to evaluate learning and memory abilities.Hematoxylin and eosin(HE)staining was used to examine morphological changes in hippocampal tissues.Enzyme‑linked immunosorbent assay(ELISA)was employed to measure serum levels of TNF‑αand IL‑1β.Western blotting and immunofluorescence staining were utilized to assess the co‑expression levels of NF‑κB p65,NLRP3,and Caspase‑1 proteins in the hippocampal region.Results Compared with the sham‑operated group,rats in the post‑modeling group exhibited significantly prolonged escape latency(P<0.05),reduced crossings of the original platform location,and decreased time spent in the target quadrant(P<0.05).Additionally,nuclear morphology was altered,neurons surrounding the hippocampus displayed necrosis,vacuolar degeneration,and chromatin marginalization.Serum levels of TNF‑αand IL‑1βwere elevated(P<0.05),and protein expression levels as well as fluorescent positivity for NF‑κB p65,NLRP3,and caspase‑1 in the hippocampus were increased(P<0.05).Compared with t

关 键 词：阿尔茨海默病 电针 NF-κB/NLRP3/Caspase-1信号通路 神经炎症 

分 类 号：R245[医药卫生—针灸推拿学]