Effect of Suanzaoren Tang on Learning Memory and TLR4/NF-<italic style="font-style: italic">κB</italic> Signaling Pathway in Rats with Chronic Sleep Deprivation

Dong-nan WU; Rui-cong DING; Ke JI; Ping WANG; Ling LIU

doi:10.13422/j.cnki.syfjx.20200501

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

Classic Prescriptions | 更新时间：2021-02-09

- Effect of Suanzaoren Tang on Learning Memory and TLR4/NF-κB Signaling Pathway in Rats with Chronic Sleep Deprivation
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 6, Pages: 18-24(2020)
- 作者机构：
  
  湖北中医药大学，武汉　 430065
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20200501
  CLC： R2-0; R22; R285.5; R289
- Received：12 August 2019，
  
  Published Online：27 November 2019，
  
  Published：20 March 2020
- 稿件说明：
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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：

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

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⁰

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