【摘要】 目的:探究栀子苷（Gen）对睡眠剥夺大鼠Toll样受体4/核因子κB（TLR4/NF-κB）信号通路及认知功能障碍的影响。方法:120只Wistar大鼠随机分为对照（NC）组、模型（M）组、Gen低剂量(Gen-L,5 g·kg^-1·d^-1)、Gen中剂量(Gen-M,10 g·kg^-1·d^-1)、Gen高剂量(Gen-H,20 g·kg^-1·d^-1)组和Gen-H+LPS(0.4 mg·kg^-1·d^-1,尾静脉注射)组,每组20只,干预7 d后,M组、Gen-L、Gen-M、Gen-H组和Gen-H+LPS组采用改良小平台水环境法制备大鼠剥夺睡眠模型。检测Morris水迷宫实验的逃避潜伏期及Y迷宫实验的行为正确率;HE染色检测大脑海马区神经元形态变化;ELISA检测各组大鼠血清S100B和神经元特异性烯醇化酶（NSE）表达水平,以及海马白细胞介素1β（IL-1β）、IL-6和肿瘤坏死因子α（TNF-α）水平;RT-qPCR检测海马TLR4及NF-κB p65 mRNA水平;Western blot检测海马TLR4及NF-κB p65蛋白表达量。结果:与NC组比较,M组大鼠逃避潜伏期,血清S100B和NSE表达水平,海马IL-1β、IL-6和TNF-α含量,以及TLR4和NF-κB p65 mRNA和蛋白表达量均显著增加（P<0.01）,行为正确率显著降低（P<0.01）;与M组比较,Gen-L、Gen-M和Gen-H组大鼠逃避潜伏期,海马IL-1β、IL-6和TNF-α含量,以及TLR4和NF-κB p65 mRNA和蛋白表达量依次降低（P<0.01）,行为正确率依次增加（P<0.01）;与Gen-H组比较,Gen-H+LPS组大鼠逃避潜伏期,血清S100B和NSE表达水平,海马IL-1β、IL-6和TNF-α含量,以及TLR4和NF-κB p65 mRNA和蛋白表达量均显著增加（P<0.01）,行为正确率显著降低（P<0.01）。结论:栀子苷可能通过抑制TLR4/NF-κB p65信号通路减轻海马炎症反应从而改善睡眠剥夺大鼠认知功能。更多还原

【Abstract】 AIM:To investigate the effects of geniposide（Gen）on Toll like receptor 4/nuclear factor-κB（TLR4/NF-κB）signaling pathway and cognitive dysfunction in sleep deprived rats.METHODS:Wistar rats（n=120）were randomly divided into normal control（NC）group,model（M）group,low-dose(5 g·kg^-1·d^-1)Gen（Gen-L）group,medium-dose(10 g·kg^-1·d^-1)Gen（Gen-M）group,high-dose(20 g·kg^-1·d^-1)Gen（Gen-H）group and Gen-H+LPS(0.4 mg·kg^-1·d^-1,tail vein injection)group.After 7 days of intervention,the sleep deprivation model of rats in M group,GenL,Gen-M,Gen-H and Gen-H+LPS group was established by improved small platform water environment.The escape latency of Morris water maze experiment and the behavior correct rate of Y maze experiment were measured.The serum levels of S100 B and neuron-specific enolase（NSE）,and the levels of interleukin-1β（IL-1β）,IL-6 and tumor necrosis factor-α（TNF-α）in hippocampus were detected by ELISA.The mRNA levels of TLR4 and NF-κB p65 were detected by RT-qPCR,and the protein levels of TLR4 and NF-κB p65 were determined by Western blot.RESULTS:Compared with NC group,the escape latency,the serum levels of S100 B and NSE,the hippocampal levels of IL-1β,IL-6 and TNF-α,and the mRNA and protein expression of TLR4 and NF-κB p65 were increased significantly in M group（P<0.01）,and the behavior correct rate was decreased significantly（P<0.01）.Compared with M group,the escape latency,the hippocampal levels of IL-1β,IL-6 and TNF-α,and the expression of TLR4 and NF-κB p65 at mRNA and protein levels were decreased significantly in Gen-L,Gen-M and Gen-H groups（P<0.01）,and the behavior correct rate was increased in turn（P<0.01）.Compared with Gen-H group,the escape latency,the serum levels of S100 B and NSE,the hippocampal levels of IL-1β,IL-6 and TNF-α,and the expression of TLR4 and NF-κB p65 at mRNA and protein levels were increased significantly in Gen-H+LPS group（P<0.01）,and the behavior correct rate was decreased significantly（P<0.01）.CONCLUSION:Geniposide may inhibit the TLR4/NF-κB p65 signaling pathway to effectively improve cognitive function in sleepdeprived rats and reduce hippocampus inflammation.更多还原