The Effect of Semen Ziziphi Spinosae Extract on the p38MAPK/NF-κB Signaling Pathway in Insomniac Rats  

酸枣仁提取物对失眠大鼠p38MAPK/NF-κB信号通路的作用

作　　者：Mingyu Ji Wei Xiong Zijing Xu Peipei Zhang Shuyu Li Qian Wang Dexian Jia 纪明宇;熊伟;许子敬;张佩佩;李姝玉;王谦;贾德贤(北京中医药大学,北京102401)

机构地区：[1]College of Chinese Medicine,Beijing University of Chinese Medicine,Beijing,China

出　　处：《Chinese Medicine and Natural Products》2024年第4期145-152,共8页中医学报(英文)

基　　金：funded by the Research on the Mechanism of Suan Zao Ren’s(Semen Ziziphi Spinosae)Hypnotic Effect Based on TXNIP/NLRP3 Signaling Pathway(2023-ZXFZJJ-JW-071).

摘　　要：Objective The objective of the study was to explore whether Suanzaoren(Semen Ziziphi Spinosae,SZS)extract could improve insomnia by inhibiting the p38 mitogenactivated protein kinase(p38MAPK)/nuclear factor-κB(NF-κB)signaling pathway.Methods Forty SPF-grade Sprague-Dawley(SD)rats were included in the study,with 10 randomly selected rats serving as the control group.The remaining rats were injected intraperitoneally with p-chlorophenylalanine(PCPA)for 6 days to establish an insomnia model.After successful modeling,the rats were divided into the model group,SZS extract group(3.0 g/kg),and zopiclone group(1.25 g/kg).The rats in the SZS extract and zopiclone groups were administered with the corresponding drugs via gavage for 7 days,while the rats in the control and model groups received distilled water.Sleep latency and sleep duration were recorded,and behavioral changes were observed through elevated plusmaze and open field tests.The levels of oxidative stress markers and serum inflammatory factors were measured by enzyme-linked immunosorbent assay(ELISA).The expression levels of p38 MAPK,p-p38MAPK,p-NF-κBp65,and NF-κBp65 protein in the cerebral cortex were detected by Western blot.Neuronal structures in the cerebral cortex were observed under a transmission electron microscope.Results Compared with the control group,the model group exhibited abnormal appearances,significant body mass loss(p<0.001),prolonged sleep latency and shortened sleep duration(p<0.001).The SZS extract and zopiclone groups showed significant improvements in these parameters compared with the model group.Compared with the control group,the model group showed significant reduction in total movement distance(p<0.001),fewer entries into the central zone(p<0.01),and significant decrease in rearing frequency(p<0.001);the levels of glutathione peroxidase(GSH-Px)and catalase(CAT)in the hippocampus were significantly reduced(p<0.001);the serum levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and the expression levels of p-p38MAPK目的:探讨酸枣仁(Semen Ziziphi Spinosae,SZS)提取物是否通过抑制p38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38MAPK)/核因子κB(nuclear factor-κB,NF-κB)信号通路改善失眠。方法:40只SPF级SD大鼠,随机选取10只作为对照组。其余大鼠通过腹腔注射对氯苯丙氨酸(p-chlorophenylalanine,PCPA)6天建立失眠模型。模型建立成功后,将大鼠分为模型组、SZS提取物组(3.0g·kg^(-1))和佐匹克隆组(1.25g·kg^(-1))。SZS提取物组和佐匹克隆组大鼠灌胃给药7天,对照组和模型组大鼠给予蒸馏水。记录大鼠睡眠潜伏期和睡眠持续时间,并通过高架十字迷宫和旷场实验观察行为变化。通过ELISA检测氧化应激标志物和血清炎症因子的水平。Western blot检测大鼠大脑皮层中p38MAPK、p-p38MAPK、p-NF-κBp65和NF-κBp65蛋白表达水平。透射电子显微镜观察大脑皮层的神经元结构。结果:与对照组相比,模型组大鼠表现出外观异常、体质量显著下降(P<0.001)、睡眠潜伏期延长和睡眠持续时间缩短(P<0.001)。与模型组相比,SZS提取物组和佐匹克隆组显著改善上述指标。与对照组相比,模型组大鼠的运动距离显著缩短(P<0.001),进入中心区的次数显著减少(P<0.01),站立频率显著下降(P<0.001);海马中谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)和过氧化氢酶(catalase,CAT)的水平显著降低(P<0.001);血清中白介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumornecrosisfactor-α,TNF-α)的水平以及大脑皮层中p-p38MAPK、p-NF-κBp65的表达水平显著升高(P<0.05)。与模型组相比,SZS提取物组大鼠的运动距离显著增加(P<0.01),站立频率显著升高(P<0.001),GSH-Px和CAT水平显著提高(P<0.001),IL-1β和TNF-α水平显著降低(P<0.01),p-p38MAPK和p-NF-κBp65水平显著降低(P<0.05),大脑皮层神经元结构显著改善。结论:SZS提取物可通过抑制p38MAPK/NF-KB信号通路改善失眠。

关 键 词：Semen Ziziphi Spinosae extract p38MAPK/NF-κB signaling pathway INSOMNIA oxidative stress inflammatory factors 

分 类 号：R28[医药卫生—中药学]