基于HMGB1-RAGE信号通路探究川芎嗪结合电针对阿尔茨海默症大鼠的神经保护作用  

Study of the neuroprotective effect of Tetramethylpyrazine combined with electroacupuncture on Alzheimer’s disease rats based on the HMGB1-RAGE signaling pathway

作　　者：何诚 王颖[1] HE Cheng;WANG Ying(Department of Rehabilitation Science,The Central Hospital of Wuhan,Tongji Medical College of Huazhong University of Science&Technology,Wuhan,Hubei 430000,China)

机构地区：[1]华中科技大学同济医学院附属武汉中心医院,武汉430000

出　　处：《上海针灸杂志》2025年第3期347-354,共8页Shanghai Journal of Acupuncture and Moxibustion

基　　金：武汉市卫生计生委办公室中医类科研项目(WZ21Z02);武汉市中心医院学科基金项目(2021XK046)。

摘　　要：目的探讨川芎嗪联合电针(electroacupuncture,EA)对阿尔茨海默病(Alzheimer’s disease,AD大鼠的神经保护作用及对高迁移率族蛋白1(high mobility group protein 1,HMGB1)/晚期糖基化终末产物受体(advanced glycosylation end-product receptor,RAGE)信号通路的影响。方法构建AD大鼠模型,将所有实验大鼠分为对照组、模型组、川芎嗪组、电针组、川芎嗪+电针组、川芎嗪+电针+HMGB1重组蛋白组,Morris水迷宫实验检测大鼠学习记忆和空间探索能力,酶联免疫吸附测定检测大鼠海马肿瘤坏死因子α(tumor necrosis factor alpha,TNF-α)、白介素-1β(interleukin-1β,IL-1β)水平,苏木精-伊红染色观察海马组织形态学变化,免疫组化检测大鼠β淀粉样蛋白1-42(beta-amyloid 1-42,Aβ1-42)、磷酸化Tau(p hosphorylated Tau,p-Tau)蛋白表达,免疫印迹检测HMGB1、RAGE蛋白表达情况。结果与对照组比较,模型组大鼠逃避潜伏期增长(P<0.05),穿越平台次数减少(P<0.05),平台停留时间减短(P<0.05),海马神经元排列紊乱,神经元大量丢失及变性坏死,核固缩,TNF-α、IL-1β、Aβ1-42、p-Tau、HMGB1和RAGE表达升高(P<0.05);与模型组比较,川芎嗪组和电针组大鼠逃避潜伏期减短(P<0.05),穿越平台次数增多(P<0.05),平台停留时间增长(P<0.05),海马神经元损伤减轻,TNF-α、IL-1β、Aβ1-42、p-Tau、HMGB1和RAGE表达降低(P<0.05);与川芎嗪组和电针组比较,川芎嗪+电针组大鼠逃避潜伏期减短(P<0.05),穿越平台次数增多(P<0.05),平台停留时间增长(P<0.05),海马神经元损伤减轻,TNF-α、IL-1β、Aβ1-42、p-Tau、HMGB1和RAGE表达降低(P<0.05);与川芎嗪+电针组比较,川芎嗪+电针+HMGB1重组蛋白组大鼠逃避潜伏期增长(P<0.05),穿越平台次数减少(P<0.05),平台停留时间减短(P<0.05),海马神经元损伤加重,TNF-α、IL-1β、Aβ1-42、p-Tau、HMGB1和RAGE表达升高(P<0.05)。结论川芎嗪联合电针治疗可以通过抑制HMGB1/RAGE信号通路保护AD大鼠神经�Objective To explore the neuroprotective effect of Tetramethylpyrazine plus electroacupuncture(EA)on Alzheimer’s disease(AD)rats and its effect on the high mobility group protein 1(HMGB1)/advanced glycosylation end-product receptor(RAGE)signaling pathway.Method AD rat models were established.The experimental rats were divided into a control group,a model group,a Tetramethylpyrazine group,an EA group,a Tetramethylpyrazine+EA group,and a Tetramethylpyrazine+EA+HMGB1 group.The Morris water maze test was used to assess the rat’s learning,memory,and spatial exploration abilities;the enzyme-linked immunosorbent assay was adopted to detect the levels of tumor necrosis factor-a(TNF-a)and interleukin-1b(IL-1b)in the rat’s hippocampal;hematoxylin-eosin(HE)staining was employed to observe morphological changes in the hippocampal tissue;immunochemistry was used to check the protein expression of beta-amyloid 1-42(Ab1-42)and phosphorylated Tau(p-Tau);the protein expression of HMGB1 and RAGE was determined using Western blot(WB).Result Compared to the control group,rats in the model group showed a longer escape latency(P<0.05),decreased platform crossings(P<0.05),reduced platform dwell time(P<0.05),disordered hippocampal neuron arrangement with significant loss and degeneration of neurons and pyknosis,and increased expression of TNF-a,IL-1b,Ab1-42,p-Tau,HMGB1,and RAGE(P<0.05).Compared to the model group,rats in the Tetramethylpyrazine and EA groups showed a shortened escape latency(P<0.05),increased platform crossings(P<0.05),longer platform dwell time(P<0.05),reduced hippocampal neuron damage,and reduced expression of TNF-a,IL-1b,Ab1-42,p-Tau,HMGB1,and RAGE(P<0.05).Compared to the Tetramethylpyrazine and EA groups,the Tetramethylpyrazine+EA group showed a shortened escape latency(P<0.05),increased platform crossings(P<0.05),longer platform dwell time(P<0.05),reduced hippocampal neuron damage,and decreased expression of TNF-a,IL-1b,Ab1-42,p-Tau,HMGB1,and RAGE(P<0.05).Compared to the Tetramethylpyrazine+EA group,rats in t

关 键 词：电针 针药并用 阿尔茨海默病 川芎嗪 高迁移率族蛋白1/晚期糖基化终末产物受体信号通路 大鼠 

分 类 号：R2-03[医药卫生—中医学]