天王补心丹加减对睡眠剥夺大鼠学习记忆及炎症因子表达的影响  

Effect of Modified Tianwang Buxindan on Learning and Memory Function and Expression of Inflammatory Factors in Sleep Deprived Rats

作　　者：黄晓宇 谢光璟 李浩[1,2] 朱愽宽 高寒 黄攀攀 HUANG Xiao-yu;XIE Guang-jing;LI Hao;ZHU Bo-kuan;GAO Han;HUANG Pan-pan(Hubei University of Chinese Medicine,Wuhan 430065,China;712 Research Institute Hospital,China Shipbuilding Industry Corporation,Wuhan 430065,China)

机构地区：[1]湖北中医药大学,武汉430065 [2]中国船舶重工集团公司第七一二研究所,武汉430065

出　　处：《中国实验方剂学杂志》2020年第23期56-62,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金面上项目(81874414);武汉市科技计划项目(2019020701011433)。

摘　　要：目的:通过研究天王补心丹对睡眠剥夺模型大鼠睡眠质量、认知功能、炎症因子及免疫相关基因表达的影响,探讨天王补心丹对睡眠剥夺状态下学习记忆过程产生干预及发挥抗炎作用的可能机制。方法:40只雄性SPF级大鼠采用多平台水环境法模拟睡眠剥夺模型,随机分为模型组,天王补心丹组(20 g·kg-1),艾司唑仑组(0.1 mg·kg-1),另设空白组,每组10只。共予以4周的睡眠剥夺造模,后2周进行药物干预,模型组与空白组灌服等体积纯水。脑电图(EEG)评估造模情况、分析大鼠睡眠结构及质量;Morris水迷宫定位航行与空间探索实验分析大鼠学习记忆能力;采用酶联免疫吸附测定(ELISA)检测血清中炎症因子白细胞介素-1β(IL-1β),肿瘤坏死因子-α(TNF-α),单核细胞趋化因子-1(MCP-1)的表达;应用实时荧光定量聚合酶链式反应(Real-time PCR)检测EB病毒诱导基因3(EBI3),细胞外信号调节激酶5(ERK5),p21活化蛋白激酶4(PAK4)的mRNA表达水平。结果:睡眠剥夺模型造模成功,与空白组比较,模型组大鼠的总睡眠时间,慢波睡眠总时长与慢波睡眠第1,第2阶段时长均明显缩短(P<0.01),上平台潜伏期、游泳总路程和第1次抵达原平台时间明显增加,而穿越平台次数和目标象限时间明显减少(P<0.05,P<0.01),血清中IL-1β,TNF-α,MCP-1水平显著上升(P<0.01),大鼠下丘脑中EBI3,ERK5与PAK4的mRNA表达水平显著下降(P<0.01);与模型组比较,天王补心丹组大鼠的睡眠质量改善明显,总睡眠时间,慢波睡眠总时长与慢波睡眠第1阶段时长显著增加(P<0.01),认知能力有一定的提升,上平台潜伏期、游泳总路程和第1次抵达原平台时间缩短,穿越平台次数和目标象限时间明显延长(P<0.05,P<0.01);血清中IL-1β,TNF-α,MCP-1水平明显降低(P<0.05,P<0.01),大鼠下丘脑中EBI3,ERK5与PAK4的mRNA表达水平明显升高(P<0.05,P<0.01)。结论:天王补心丹可提高睡眠剥夺模型大鼠的睡眠质量与Objective: By studying the effects of Tianwang Buxindan on sleep quality,cognitive function,inflammatory factors and immune-related gene expression in sleep deprivation model rats,explore the effect of Tianwang Buxindan on the learning and memory process under sleep deprivation and its anti-inflammatory effects possible mechanism. Method: The 40 male SPF rats were used to simulate the sleep deprivation model by multi-platform water environment method,and were randomly divided into model group,Tianwang Buxindan group(20 g·kg-1)and estazolam group(0.1 mg·kg-1),set up a normal group,10 in each group. A total of 4 weeks of sleep deprivation modeling was performed,and drug intervention was performed 2 weeks later. The model group and the blank group were given equal volumes of pure water.Electroencephalogram(EEG)evaluation of modeling and analysis of sleep structure and quality of rats,Morris water maze positioning navigation and space exploration experiment analysis of learning and memory ability of rats,application of enzyme-linked immunosorbent assay(ELISA)was used to detect the serum inflammatory factor interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),monocyte chemokine-1(MCP-1)expression,Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)was used to detect the mRNA levels of EB virus inducible gene 3(EBI3),extracellular signal-regulated kinase 5(ERK5),and p21 activated protein kinase 4(PAK4). Result: The sleep deprivation model was successfully built. Compared with blank group,the total sleep time,total duration of slow wave sleep and the duration of the first and second phases of slow wave sleep in the model group were significantly shortened(P<0.01). The incubation period on the upper platform,the total swimming distance and the time to reach the original platform for the first time increased significantly,while the number of times to cross the platform and the target quadrant significantly decreased(P<0.05,P<0.01). The expression levels of IL-1β,TNF-α and MCP-1 increased si

关 键 词：天王补心丹 睡眠剥夺 认知功能 炎症 炎症因子 

分 类 号：R2-0[医药卫生—中医学] R289