天王补心丹对卒中后失眠模型大鼠的改善作用及机制研究  

Effect and mechanism of Tianwang Buxin Dan on insomnia model rats after stroke

作　　者：马小涵 杨嘉誉 汤文政 林如辉 MA Xiaohan;YANG Jiayu;TANG Wenzheng;LIN Ruhui(Institute of Integrative Chinese and Western Medicine,Fujian University of Chinese Medicine,Fuzhou 350122,China;Science and Technology Innovation and Transformation Center,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;College of Acupuncture and Massage,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)

机构地区：[1]福建中医药大学中西医结合学院(中西医结合研究院),福建福州350122 [2]福建中医药大学科技创新与转化中心,福建福州350122 [3]福建中医药大学针灸推拿学院,福建福州350122

出　　处：《广东药科大学学报》2025年第1期108-116,共9页Journal of Guangdong Pharmaceutical University

基　　金：福建省自然科学基金项目(2023J01873,2022J01878)。

摘　　要：目的探讨天王补心丹对卒中后失眠模型大鼠的改善作用及机制。方法构建卒中后失眠大鼠模型,分为正常组、模型组、天王补心丹低(1.9 g/kg)、高(7.6 g/kg)剂量组,干预7 d。干预前后通过Zea-Longa神经功能评分及翻正实验观察大鼠神经功能缺损情况和睡眠状况的变化情况;干预第3天至第6天采用水迷宫定位航行实验,干预第7天采用水迷宫空间探索实验和新物体识别实验,观察大鼠学习记忆能力;通过核磁共振T2WI加权成像技术及波谱技术(MRS)检测脑梗面积和下丘脑区肌醇(MI)、胆碱(Cho)、γ-氨基丁酸(GABA)、谷氨酸(Glu)表达水平;Elisa法检测血清白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)及肿瘤坏死因子-α(TNF-α)水平;q-PCR和Western blot法检测下丘脑区肌肉芳香烃受体核转位样蛋白1(Bmal1)、离子钙结合适配器分子1(Iba1)等相关基因及蛋白的表达水平。结果与模型组比较,天王补心丹各剂量组神经功能评分降低,睡眠潜伏期缩短,睡眠时长延长(P<0.05);逃避潜伏期下降,穿越逃生平台次数增多(P<0.05);新物体识别指数增加(P<0.05);脑梗面积减少,下丘脑区Cho和GABA代谢物水平降低,高剂量组大鼠MI下降(P<0.05),低剂量组有所降低;血清中IL-1β、IL-6及TNF-α下降,IL-10增高(P<0.05);Bmal1蛋白及基因表达量上调,Iba1蛋白及基因表达量下降(P<0.05)。结论天王补心丹可调节卒中后失眠模型大鼠的睡眠状态与炎症反应,改善学习认知与空间记忆能力,对卒中后失眠有较好疗效。Objective To investigate the effect and mechanism of Tianwang Buxin Dan on insomnia model rats after stroke.Methods A post-stroke insomnia rat model was established and divided into normal group,model group,Tianwang Buxindan low(1.9 g/kg)and high(7.6 g/kg)dose groups.The intervention lasted for 7 days.Neurological function deficit and sleep status were observed before and after the intervention by Zea-Longa nerve function score and righting test.On the 3rd to 6th day of intervention,water maze navigation experiment was used,and on the 7th day,water maze space exploration experiment and new object recognition experiment were used to observe the learning and memory ability of rats.Cerebral infarction area and the expression levels of inositol(MI),choline(Cho),gamma-aminobutyric acid(GABA)and glutamic acid(Glu)in hypothalamus were detected by weighted MRI T2WI imaging and NMR spectroscopy(MRS).Serum levels of interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-10(IL-10)and tumor necrosis factor-α(TNF-α)were detected by Elisa.The expression levels of Muscle aromatic hydrocarbon receptor nuclear translocation-like protein 1(Bmal1),ionic Calcium binding adaptor molecule 1(Iba1)and other related genes and proteins in hypothalamus were detected by q-PCR and western blot.Results Compared with the model group,the neural function scores were decreased,sleep latency was shortened,and sleep duration was prolonged was decreased in rats treated with Tianwang Buxin Dan(P<0.05).Meantime,the latency of escape decreased and the number of escape platform crossings increased(P<0.05).New object recognition index increased(P<0.05).Cerebral infarction area was decreased,The levels of Cho and GABA metabolites in hypothalamus decreased,and MI decreased in high-dose group(P<0.05),the low dose group was decreased.The levels of serum IL-1β,IL-6 and TNF-αwere decreased,while IL-10 was increased(P<0.05).The expression of Bmal1 protein and gene was upregulated,and the expression of Iba1 protein and gene was lowered(P<0.05).Conclusion Ti

关 键 词：卒中后失眠 天王补心丹 睡眠节律 炎症反应 认知记忆能力 

分 类 号：R965[医药卫生—药理学]