Effect of Modified Buwangsan on Expression of Related Molecules in NLRP3 Inflammatory Signaling Pathway in Hippocampus of AD Rats

Ling-ling HE; Xiao-qiong LI; Xiao-lei LIU; Miao-miao HOU; Xin-yi LI

doi:10.13422/j.cnki.syfjx.20200239

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Effect of Modified Buwangsan on Expression of Related Molecules in NLRP3 Inflammatory Signaling Pathway in Hippocampus of AD Rats

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- Effect of Modified Buwangsan on Expression of Related Molecules in NLRP3 Inflammatory Signaling Pathway in Hippocampus of AD Rats
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 4, Pages: 35-41(2020)
- 作者机构：
  
  1.山西医科大学　附属大医院，太原　 030000
  2.安徽医科大学　附属巢湖医院，合肥　 230031
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20200239
  CLC： R2-0; R289; R285.5
- Received：10 January 2019，
  
  Published Online：09 October 2019，
  
  Published：20 February 2020
- 稿件说明：
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Ling-ling HE, Xiao-qiong LI, Xiao-lei LIU, et al. Effect of Modified Buwangsan on Expression of Related Molecules in NLRP3 Inflammatory Signaling Pathway in Hippocampus of AD Rats[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(4): 35-41.
DOI：

Ling-ling HE, Xiao-qiong LI, Xiao-lei LIU, et al. Effect of Modified Buwangsan on Expression of Related Molecules in NLRP3 Inflammatory Signaling Pathway in Hippocampus of AD Rats[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(4): 35-41. DOI： 10.13422/j.cnki.syfjx.20200239.

摘要

目的：

通过观察加味不忘散对阿尔茨海默病(AD)模型大鼠学习记忆能力及海马区NOD样受体热蛋白结构域3(NLRP3)炎症通路中相关分子NLRP3，天冬氨酸蛋白酶-1(Caspase-1)和白细胞介素-1

(IL-1

)表达的影响，探讨其作用机制。

方法：

通过Morris水迷宫筛选出合格SD大鼠52只，随机均分为假手术组，AD模型组，加味不忘散低剂量组(1.5 g·kg

-1

)，加味不忘散高剂量组(3 g·kg

-1

)。采用双侧海马注射

-淀粉样蛋白1-42(A

1-42

)5 μL (2 g·L

-1

)建立AD模型大鼠。造模后分别予低、高剂量加味不忘散灌胃，每日1次，连续4周。灌胃结束后通过Morris水迷宫法检测大鼠学习记忆能力，判断造模是否成功；通过实时荧光定量聚合酶链式反应(Real-time PCR)，蛋白免疫印迹法(Western blot)检测大鼠海马组织中NLRP3，Caspase-1，IL-1

mRNA和蛋白的表达水平。

结果：

与假手术组比较，AD模型组大鼠学习记忆能力明显下降(

0.05)；与AD模型组比较，加味不忘散低剂量组大鼠学习记忆能力无改善，NLRP3，Caspase-1，IL-1

mRNA和蛋白的表达水平均无统计学差异，加味不忘散高剂量组大鼠学习记忆能力明显改善，NLRP3，Caspase-1，IL-1

mRNA和蛋白的表达均明显下降(

0.05)。

结论：

高剂量加味不忘散可改善大鼠学习记忆能力，其机制可能与下调NLRP3炎症通路中NLRP3及下游Caspase-1，IL-1

的表达，抑制海马组织内的炎症反应有关。

Abstract

Objective:

To investigate the effects of modified Buwangsan on the learning and memory ability of Alzheimer's disease (AD) model rats and the expression of NOD-like receptor 3 (NLRP3)

cysteine-containing aspartate-specific proteases 1 (Caspase-1) and interleukin-1 beta (IL-1

) in NLRP3 inflammatory pathway in hippocampus of AD model rats

and exploring the underlying mechanism of modified Buwangsan.

Method:

The 52 eligible rats were randomly divided into sham control group

AD model group

low-dose modified Buwangsan group (1.5 g·kg

-1

) and high-dose modified Buwangsan group (3 g·kg

-1

). AD mouse model was established by bilateral hippocampus injection of A

1-42

5 μL (2 g·L

-1

). The rats in low-dose and high-dose modified Buwangsan group received low and high dose modified Buwangsan respectively within the next 4 weeks

once daily. The learning and memory ability was tested by Morris water maze. The expression of NLRP3

Caspase-1 and IL-1

mRNA was tested by quantitative PCR(Real-time PCR) and Western blot.

Result:

As compared with the sham group

the learning and memory ability of the rats were significantly impaired (

0.05). Compared with AD model group

the learning and memory ability and the expression levels of NLRP3

Caspase-1

and IL-1

mRNA and protein were all no statistical differences in low-dose modified Buwangsan group

while the learning and memory ability of the rats were significantly improved and the expression of NLRP3

Caspase-1 and IL-1

mRNA in hippocampus of rats was significantly decreased in high-dose modified Buwangsan group (

0.05).

Conclusion:

High-dose modified Buwangsan could attenuate neuroinflammation in the hippocampus of AD mouse model via inhibiting the expression of NLRP3

Caspase-1 and IL-1

which may be the mechanisms of modified Buwangsan could be used to ameliorate the learning and memory ability of AD mouse model.

关键词

Keywords

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