摘要
目的:基于Toll样受体4(TLR4)/核转录因子-κB(NF-κB)信号通路探讨酸枣仁汤改善睡眠剥夺诱导学习记忆障碍的作用机制。方法:将实验大鼠随机分为正常组、模型组、褪黑素组(2. 5×10-4g·kg-1·d-1)和酸枣仁汤组(12. 96 g·kg-1·d-1),除正常组外,其他各组构建慢性睡眠剥夺模型。各组连续给药28 d后,采用Morris水迷宫评价大鼠的学习记忆力,采用酶联免疫吸附测定法(ELISA)检测大鼠血清中白细胞介素-1β(IL-1β),白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)表达水平,采用实时荧光定量聚合酶链式反应(Real-time PCR)法检测大鼠海马中TLR4,NF-κB p65及核转录因子抑制蛋白α(IκBα)的m RNA表达水平,采用免疫组化(IHC)检测大鼠海马中TLR4,IκBα,p-IκBα和NF-κB p65的蛋白表达水平。结果:与正常组比较,模型组大鼠上平台潜伏期、游泳总路程和第1次抵原平台时间明显增加(P <0. 01),而穿越平台次数和目标象限时间显著减少(P <0. 01);与模型组比较,褪黑素组和酸枣仁汤组大鼠上平台潜伏期、游泳总路程和第1次抵原平台时间减少(P <0. 05,P <0. 01),而穿越平台次数和目标象限时间增加(P <0. 05,P <0. 01)。与正常组比较,模型组大鼠血清中TNF-α,IL-1β,IL-6表达水平显著升高(P <0. 01);与模型组比较,褪黑素组和酸枣仁汤组大鼠血清中TNF-α,IL-1β,IL-6表达水平下降(P <0. 05,P <0. 01)。与正常组比较,模型组大鼠海马中TLR4,NF-κB p65 m RNA及蛋白表达水平升高(P <0. 01),而IκBαm RNA及蛋白表达水平下降(P <0. 01)。与模型组比较,褪黑素组和酸枣仁汤组大鼠海马中TLR4,NF-κB p65 m RNA及蛋白表达水平降低(P <0. 05,P <0. 01),而IκBαm RNA及蛋白表达水平升高(P <0. 05,P <0. 01)。与正常组比较,模型组大鼠海马中p-IκBα的蛋白表达水平显著升高(P <0. 01);与模型组比较,褪黑素组和酸枣仁汤组大鼠海马中IκBα的蛋白表达水平升高(P <0. 05,P <0. 01)。结论:酸枣�
Objective: To explore the mechanism of Suanzaoren Tang in improving learning and memory impairment induced by sleep deprivation based on Toll-like receptor( TLR4)/nuclear transcription factor-κB( NF-κB) signaling pathway. Method: The experimental rats were randomly divided into blank group,model group,melatonin group( 2. 5 × 10-4 g·kg-1·d-1) and Suanzaoren Tang group( 12. 96 g·kg-1·d-1). Except the blank group,the chronic sleep deprivation model was established in other groups. After 28 days of continuous administration,the learning and memory of the rats were assessed by Morris water maze. The expressions of interleukin-1β( IL-1β),interleukin-6( IL-6) and tumor necrosis factor-α( TNF-α) in serum were detected by enzyme-linked immunosorbent assay( ELISA). The m RNA expression levels of TLR4,NF-κB p65 and nuclear transcription factor inhibitory protein α( IκBα) in the hippocampus of rats were detected by real-time fluorescence quantitative polymerase chain reaction( Real-time PCR),and the protein expressions of TLR4,IκBα,p-IκBα and NF-κB p65 in the hippocampus of rats were detected by immunohistochemistry( IHC). Result: Compared with the blank group,the platform latency,total swimming distance and the first landing time of the model group increased significantly( P < 0. 01),while the number of crossing platforms and target quadrant time decreased significantly( P < 0. 01). Compared with the model group,the platform latency,total swimming distance and the first platform time were reduced in the melatonin group and the Suanzaoren group( P < 0. 05,P < 0. 01),while the number of crossing platforms and target quadrants time were increased( P < 0. 05,P < 0. 01). Compared with the blank group,the expression levels of TNF-α,IL-1β and IL-6 in the model group were significantly increased( P <0. 01). Compared with the model group,the levels of TNF-α,IL-1β and IL-6 in the serum of melatonin group and Suanzaoren Tang group decreased( P < 0. 05,P < 0. 01). Compared with the blank group,m RNA and protein
作者
吴东南
丁瑞丛
纪可
王平
刘玲
WU Dong-nan;DING Rui-cong;JI Ke;WANG Ping;LIU Ling(Hubei University of Chinese Medicine,Wuhan 430065,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2020年第6期18-24,共7页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(81573865)。
