酸枣仁汤对慢性睡眠剥夺大鼠学习记忆及TLR4/NF-<italic style="font-style: italic">κ</italic>B信号通路的影响

吴东南; 丁瑞丛; 纪可; 王平; 刘玲

doi:10.13422/j.cnki.syfjx.20200501

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酸枣仁汤对慢性睡眠剥夺大鼠学习记忆及TLR4/NF-κB信号通路的影响

经典名方 | 更新时间：2021-02-09

- 酸枣仁汤对慢性睡眠剥夺大鼠学习记忆及TLR4/NF-κB信号通路的影响
- Effect of Suanzaoren Tang on Learning Memory and TLR4/NF-κB Signaling Pathway in Rats with Chronic Sleep Deprivation
- 中国实验方剂学杂志 2020年26卷第6期页码：18-24
- 作者机构：
  
  湖北中医药大学，武汉　 430065
- 作者简介：
  
  [第一作者]　吴东南，博士，从事中医药防治睡眠与认知障碍疾病的研究，E-mail：wudongnan1224@126.com
  *刘玲，博士，教授，博士生导师，从事中医脑病的研究，Tel：027-88929230，E-mail: lingliu07199@aliyun.com
- 基金信息：
  
  国家自然科学基金项目(81573865)
- DOI：10.13422/j.cnki.syfjx.20200501
  中图分类号： R2-0; R22; R285.5; R289
- 收稿日期：2019-08-12，
  
  网络出版日期：2019-11-27，
  
  纸质出版日期：2020-03-20
- 稿件说明：
移动端阅览
吴东南, 丁瑞丛, 纪可, 等. 酸枣仁汤对慢性睡眠剥夺大鼠学习记忆及TLR4/NF-κB信号通路的影响[J]. 中国实验方剂学杂志, 2020,26(6):18-24.

Dong-nan WU, Rui-cong DING, Ke JI, et al. Effect of Suanzaoren Tang on Learning Memory and TLR4/NF-κB Signaling Pathway in Rats with Chronic Sleep Deprivation[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(6): 18-24.
吴东南, 丁瑞丛, 纪可, 等. 酸枣仁汤对慢性睡眠剥夺大鼠学习记忆及TLR4/NF-κB信号通路的影响[J]. 中国实验方剂学杂志, 2020,26(6):18-24. DOI： 10.13422/j.cnki.syfjx.20200501.

Dong-nan WU, Rui-cong DING, Ke JI, et al. Effect of Suanzaoren Tang on Learning Memory and TLR4/NF-κB Signaling Pathway in Rats with Chronic Sleep Deprivation[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(6): 18-24. DOI： 10.13422/j.cnki.syfjx.20200501.

摘要

目的：

基于Toll样受体4(TLR4)/核转录因子-

B(NF-

B)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

-4

g·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-1

(IL-1

)，白细胞介素-6(IL-6)和肿瘤坏死因子-

(TNF-

)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-

B p65及核转录因子抑制蛋白

)的mRNA表达水平，采用免疫组化(IHC)检测大鼠海马中TLR4，I

，p-I

和NF-

B 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(

0.01)，而穿越平台次数和目标象限时间显著减少(

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(

0.05，

0.01)，而穿越平台次数和目标象限时间增加(

0.05，

0.01)。与正常组比较，模型组大鼠血清中TNF-

，IL-1

，IL-6表达水平显著升高(

0.01)；与模型组比较，褪黑素组和酸枣仁汤组大鼠血清中TNF-

，IL-1

，IL-6表达水平下降(

0.05，

0.01)。与正常组比较，模型组大鼠海马中TLR4，NF-

B p65 mRNA及蛋白表达水平升高(

0.01)，而I

mRNA及蛋白表达水平下降(

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-

B p65 mRNA及蛋白表达水平降低(

0.05，

0.01)，而I

mRNA及蛋白表达水平升高(

0.05，

0.01)。与正常组比较，模型组大鼠海马中p-I

的蛋白表达水平显著升高(

0.01)；与模型组比较，褪黑素组和酸枣仁汤组大鼠海马中I

的蛋白表达水平升高(

0.05，

0.01)。

结论：

酸枣仁汤具有改善睡眠剥夺大鼠学习记忆的作用，其机制可能与其抑制海马中TLR4/NF-

B信号通路相关。

Abstract

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-

B (NF-

B) 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-1

(IL-1

)

interleukin-6 (IL-6) and tumor necrosis factor-

(TNF-

)in serum were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of TLR4

NF-

B p65 and nuclear transcription factor inhibitory protein

) in the hippocampus of rats were detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR)

and the protein expressions of TLR4

p-I

and NF-

B 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 (

0.01)

while the number of crossing platforms and target quadrant time decreased significantly (

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 (

0.05

0.01)

while the number of crossing platforms and target quadrants time were increased(

0.05

0.01). Compared with the blank group

the expression levels of TNF-

IL-1

and IL-6 in the model group were significantly increased (

0.01). Compared with the model group

the levels of TNF-

IL-1

and IL-6 in the serum of melatonin group and Suanzaoren Tang group decreased (

0.05

0.01). Compared with the blank group

mRNA and protein expression levels of TLR4 and NF-

B p65 in the hippocampus of the model group were increased (

0.01)

while mRNA and protein expression levels of I

were decreased (

0.01). Compared with the model group

the mRNA and protein expressions of TLR4 and NF-

B p65 in the hippocampus of melatonin group and Suanzaoren Tang group decreased (

0.05

0.01)

while the mRNA and protein expression levels of I

increased (

0.05

0.01). Compared with the blank group

the protein expression level of p-I

in the hippocampus of the model group was significantly increased (

0.01). Compared with the model group

the protein expression level of I

in the hippocampus of melatonin group and Suanzaoren Tang group was increased (

0.05

0.01).

Conclusion:

Suanzaoren Tang can improve learning and memory impairment induced by sleep deprivation in rats

and its mechanism may be related to its inhibition of TLR4/NF-

B signaling pathway in hippocampus.

关键词

Keywords

references

刘芸，董永海，李晓云，等．中国60岁以上老年人睡眠障碍患病率的Meta分析 [J]．现代预防医学， 2014 ， 41 ( 8 ): 1442 - 1445 .

E NABAEE , M KESMATI , A SHAHRIARI ， et al . Cognitive and hippocampus biochemical changes following sleep deprivation in the adult male rat [J]． Biomed Pharmacother ， 2018 ， 104 : 69 - 76 .

B ANNA , L JERZY , M A GHULAM ， et al . Sleep disorders associated with alzheimer's disease：a perspective [J]． Front Neurosci ， 2018 ， 12 : 330 .

黄庆云．酸枣仁汤治疗不寐的文献研究与Meta分析 [D]．广州：广州中医药大学， 2018 .

X NIU , B HE , Y DU ， et al . The investigation of immunoprotective and sedative hypnotic effect of total polysaccharide from Suanzaoren Tang by serum metabonomics approach [J]． J Chromatogr B ， 2018 ， 1086 : 29 - 37 .

D WU , X ZHANG , M ZHAO ， et al . The role of the TLR4/NF- κ B signaling pathway in A β accumulation in primary hippocampal neurons [J]． Acta Physiologica Sinica ， 2015 ， 67 ( 3 ): 319 - 328 .

尹超，游秋云，张美娅，等．生慧汤对慢性睡眠剥夺小鼠学习记忆及海马IL-6，TNF- α ，COX-2基因表达的影响 [J]．中国实验方剂学杂志， 2019 ， 25 ( 1 ): 96 - 100 .

龙清华，丁莉，赵宾宾，等．酸枣仁汤通过抑制APP/PS1双转基因小鼠海马神经炎症发挥神经保护作用 [J]．中国实验方剂学杂志， 2019 ， 25 ( 20 ): 1 - 6 .

J CORDEIRA , S S KOLLURU , H ROSENBLATT ， et al . Learning and memory are impaired in the object recognition task during metestrus/diestrus and after sleep deprivation [J]． Behav Brain Res ， 2018 ， 339 : 124 - 129 .

马哲，王平，游秋云．睡眠及睡眠剥夺与学习记忆的相关性探讨 [J]．中华中医药杂志， 2014 ， 29 ( 4 ): 995 - 997 .

E NABAEE , M KESMATI , A SHAHRIARI ， et al . Cognitive and hippocampus biochemical changes following sleep deprivation in the adult male rat [J]． Biomed Pharmacother ， 2018 ， 104 : 69 - 76 .

M SAYGIN , M F OZGUNER , O ONDER ， et al . The impact of sleep deprivation on hippocampal-mediated learning and memory in rats [J]． Bratisl Lek Listy ， 2017 ， 118 ( 7 ): 408 - 416 .

农汝楠，王竟静，吴燕春，等．基于TLR4信号通路的中药抗肝脏疾病作用研究进展 [J]．中国实验方剂学杂志， 2019 ， 25 ( 16 ): 201 - 212 .

G FERNÁNDEZ , M ANA , M I CUARTERO ， et al . TLR4-binding DNA aptamers show a protective effect against acute stroke in animal models [J]． Mol Ther ， 2018 ， 26 : 2047 - 2059 .

J MIRON , C PICARD , M E LAFAILLE-MAGNAN ， et al . Association of TLR4 with Alzheimer's disease risk and presymptomatic biomarkers of inflammation [J]． Alzheimer's Dement ， 2019 ， 15 : 951 - 960 .

X D ZHANG , Q Y FAN , Z QIU ， et al . MiR-7 alleviates secondary inflammatory response of microglia caused by cerebral hemorrhage through inhibiting TLR4 expression [J]． Eur Rev Med Pharmacol Sci ， 2018 ， 22 : 5597 - 5604 .

李玲美，付建华，郭浩，等．注射用红花黄色素经TLR-NF- κ B炎症通路抗大鼠MIRI的保护作用研究 [J]．中国中药杂志， 2019 ， 44 ( 12 ): 2566 - 2571 .

H FANG , H F LI , M YANG ， et al . NF-kappaB signaling pathway inhibition suppresses hippocampal neuronal apoptosis and cognitive impairment via RCAN1 in neonatal rats with hypoxic-ischemic brain damage [J]． Cell Cycle ， 2019 ， 18 : 1001 - 1018 .

Q H ZHOU , H L WANG , X L ZHOU ， et al . Efficacy and safety of suanzaoren decoction for chronic insomnia disorder in adults：study protocol for randomised，double-blind，double-dummy，placebo-controlled trial [J]． BMJ Open ， 2017 ， 7 ( 4 ): e014280 .

张如意，游秋云，王平，等．酸枣仁汤对慢性睡眠剥夺老年失眠大鼠视交叉上核c-fos及nNos表达的影响 [J]．辽宁中医杂志， 2017 ， 44 ( 10 ): 201-203，233 .

李梅，胡霖霖，张永华．加味酸枣仁汤联合佐匹克隆治疗焦虑性失眠及对5-羟色胺与多巴胺水平的影响 [J]．中国实验方剂学杂志， 2015 ， 21 ( 17 ): 161 - 164 .

郭杰，尹晓刚．酸枣仁汤对老年失眠模型大鼠学习记忆能力及脑内神经递质含量的影响 [J]．中国药房， 2016 ， 27 ( 22 ): 3085 - 3087 .

张如意，游秋云，王平，等．酸枣仁汤对慢性睡眠剥夺老年失眠大鼠视交叉上核c-fos及nNos表达的影响 [J]．辽宁中医杂志， 2017 ， 44 ( 10 ): 2211-2213，2243 .

罗丹．褪黑素对脂肪细胞内质网应激诱导炎症的影响及其分子机制研究 [D]．咸阳：西北农林科技大学， 2018 .

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酸枣仁汤对慢性睡眠剥夺大鼠学习记忆及TLR4/NF-κB信号通路的影响

Effect of Suanzaoren Tang on Learning Memory and TLR4/NF-κB Signaling Pathway in Rats with Chronic Sleep Deprivation

DOI：10.13422/j.cnki.syfjx.20200501

摘要

Abstract

关键词

Keywords

references