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顾鑫, 安晶, 张洪艳, 张明雪, 娄展.温胆汤调控p38 MAPK磷酸化对睡眠剥夺大鼠失眠及伴发不良情绪的影响[J].湖南中医药大学学报,2025,45(8):1420-1426[点击复制] |
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| 温胆汤调控p38 MAPK磷酸化对睡眠剥夺大鼠失眠及伴发不良情绪的影响 |
| 顾鑫,安晶,张洪艳,张明雪,娄展 |
| (河北北方学院附属第一医院神经内科, 河北 张家口 075000;河北北方学院附属第一医院检验科, 河北 张家口 075000;重庆市合川区中医院神经内科, 重庆 401520) |
| 摘要: |
| 目的 研究温胆汤调控p38丝裂原活化蛋白激酶（p38 MAPK）磷酸化对睡眠剥夺大鼠失眠及伴发不良情绪的影响。方法 将SD雄性大鼠随机分为对照组、模型组、西药组、低剂量温胆汤组、中剂量温胆汤组、高剂量温胆汤组，对照组不进行睡眠剥夺，其余五组进行21 d睡眠剥夺。建模成功后进行灌胃治疗，对照组和模型组给予生理盐水，西药组给予艾司西酞普兰（0.9 mg/kg·d），低、中、高剂量温胆汤组给予温胆汤（0.5 g/100 g、1 g/100 g、2 g/100 g），连续14 d。采用睡眠潜伏时间、睡眠持续时间评价失眠，采用旷场实验和蔗糖水偏好实验评价抑郁，采用高架十字迷宫实验评价焦虑，采用酶联免疫吸附法检测血清5-羟色胺（5-HT）、去甲肾上腺素（NE）、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平以及海马组织中5-HT、NE水平，采用Western blot检测脑源性神经营养因子（BDNF）表达水平及p-p65核因子-κB(NF-κB)和p38 MAPK磷酸化水平。结果 与对照组比较，模型组睡眠潜伏时间延长（P<0.05），睡眠持续时间缩短（P<0.05），旷场实验得分、蔗糖水偏好率、开臂入臂次数百分比、开臂滞留时间百分比、血清和海马组织5-HT及NE水平、海马组织BDNF表达水平降低（P<0.05），血清TNF-α、IL-6水平及海马组织p-p65 NF-κB/p65 NF-κB、p-p38MAPK/p38 MAPK蛋白表达水平比值升高（P<0.05）。与模型组比较，西药组及中、高剂量温胆汤组睡眠潜伏时间缩短，睡眠持续时间延长（P<0.05）；西药组及低、中、高剂量温胆汤组，旷场实验得分、蔗糖水偏好率、开臂入臂次数百分比、开臂滞留时间百分比、血清和海马组织5-HT及NE水平、海马组织BDNF表达水平升高，血清TNF-α、IL-6水平及海马组织p-p65 NF-κB/p65 NF-κB、p-p38 MAPK/p38MAPK蛋白表达水平比值降低（P<0.05）；西药组与高剂量温胆汤组的上述指标比较，差异无统计学意义（P>0.05）。结论 不同剂量温胆汤改善睡眠剥夺大鼠的睡眠及情绪，且高剂量温胆汤的改善作用与西药艾司西酞普兰相当；抑制p38 MAPK磷酸化是温胆汤发挥改善作用的可能分子机制。 |
| 关键词: 失眠 睡眠剥夺 抑郁 焦虑 温胆汤 p38 MAPK |
| DOI：10.3969/j.issn.1674-070X.2025.08.004 |
| 投稿时间：2025-02-14 |
| 基金项目:张家口市2024年市级科技计划自筹经费项目(2421040D) |
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| Effects of Wendan Decoction on insomnia and associated negative emotions in sleep-deprived rats via regulation of p38 MAPK phosphorylation |
| GU Xin, AN Jing, ZHANG Hongyan, ZHANG Mingxue, LOU Zhan |
| (Department of Neurology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei 075000, China;Clinical Laboratory, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei 075000, China;Department of Neurology, Chongqing Hechuan Traditional Chinese Medicine Hospital, Chongqing 401520, China) |
| Abstract: |
| Objective To investigate the effects of Wendan Decoction（WDD） on insomnia and associated negative emotions in sleep-deprived rats via regulation of p38 mitogen-activated protein kinase（p38 MAPK） phosphorylation. Methods Male SD rats were randomly divided into six groups: control, model, Western medicine, low-, medium-, and high-dose WDD groups. The control group was not subjected to sleep deprivation, while the other five groups underwent sleep deprivation for 21 days. After successful modeling, treatments were administered by gavage: animals in the control and model groups received normal saline; Western medicine group received escitalopram（0.9 mg/kg·d）; WDD groups received low, medium, or high doses（0.5 g/100 g, 1 g/100 g, 2 g/100 g） of WDD for 14 consecutive days. Sleep latency and sleep duration were measured to evaluate insomnia. The open field test and sucrose preference test were used to assess depressive-like behavior, while the elevated plus maze test was employed to evaluate anxiety-like behavior. Serum levels of 5-hydroxytryptamine（5-HT）, norepinephrine（NE）, tumor necrosis factor-α（TNF-α）,and interleukin-6（IL-6）, as well as hippocampal levels of 5-HT and NE, were determined by ELISA. The expression levels of brain-derived neurotrophic factor（BDNF）, phosphorylated p65 nuclear factor-κB（p-p65 NF-κB）, and p38 MAPK in the hippocampus were detected by Western blot analysis. Results Compared with the control group, the model group exhibited prolonged sleep latency（P＜0.05） and reduced sleep duration（P＜0.05）. The model group also had lower scores in the open field test, decreased sucrose preference rate, decreased percentage of open arm entries and time spent in open arms in the elevated plus maze test,reduced 5-HT and NE levels in serum and hippocampal tissue, and decreased hippocampal BDNF expression（P＜0.05）. Additionally,serum TNF-α and IL-6 levels, as well as the ratios of p-p65 NF-κB/p65 NF-κB and p-p38 MAPK/p38 MAPK in hippocampal tissue, were significantly increased（P＜0.05）. Compared with the model group, the Western medicine group and the medium-, and high-dose WDD groups showed reduced sleep latency and prolonged sleep duration（P＜0.05）, the Western medicine group and the low-, medium-, and high-dose WDD groups showed had higher scores in the open field test, increased sucrose preference rate,higher percentage of open arm entries and time spent in open arms, elevated levels of 5-HT and NE in serum and hippocampal tissue, and increased expression of BDNF in the hippocampus（P＜0.05）. Furthermore, serum TNF-α and IL-6 levels, as well as the ratios of p-p65 NF-κB/p65 NF-κB and p-p38 MAPK/p38 MAPK in the hippocampus, were significantly decreased（P＜0.05）. There were no significant differences in these indicators between the Western medicine group and the high-dose WDD group（P ＞0.05）. Conclusion WDD at different doses can improve sleep and emotion in sleep-deprived rats, and the effects of the high-dose WDD are comparable to those of the Western medicine escitalopram. Inhibition of p38 MAPK phosphorylation may be a potential molecular mechanism underlying the therapeutic effects of WDD. |
| Key words: insomnia sleep deprivation depression anxiety Wendan Decoction p38 MAPK |
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