逍遥散对LPS所致大鼠神经损伤的保护作用机制

石博宇; 刘蓉; 饶志粒; 刘小波; 罗杰; 纪雅菲; 刘淇; 曾南

doi:10.13422/j.cnki.syfjx.20190536

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逍遥散对LPS所致大鼠神经损伤的保护作用机制

经典名方 | 更新时间：2021-02-09

- 逍遥散对LPS所致大鼠神经损伤的保护作用机制
- Neuroprotective Effect and Mechanism of Xiaoyaosan on Lipopolysaccharide-induced Nerve Injury in Rat
- 中国实验方剂学杂志 2019年25卷第5期页码：50-56
- 作者机构：
  
  成都中医药大学，中药资源系统研究与开发利用省部共建国家重点实验室培育基地，成都　 611137
- 作者简介：
  
  石博宇，在读硕士，从事中药神经精神药理学研究，E-mail: spring729477@126.com
  曾南，教授，博士生导师，从事中药药理与毒理学研究，E-mail: zengnan966@126.com
- 基金信息：
  
  国家自然科学基金项目(81503277;81473399);四川省自然科学基金项目(16ZB0116);成都中医药大学科研基金项目(ZRQN1643)
- DOI：10.13422/j.cnki.syfjx.20190536
  中图分类号： R289;R246.6;R459.1;B845.1
- 收稿日期：2018-09-25，
  
  网络出版日期：2018-11-21，
  
  纸质出版日期：2019-03-05
- 稿件说明：
移动端阅览
石博宇, 刘蓉, 饶志粒, 等. 逍遥散对LPS所致大鼠神经损伤的保护作用机制[J]. 中国实验方剂学杂志, 2019,25(5):50-56.

Bo-yu SHI, Rong LIU, Zhi-li RAO, et al. Neuroprotective Effect and Mechanism of Xiaoyaosan on Lipopolysaccharide-induced Nerve Injury in Rat[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(5): 50-56.
石博宇, 刘蓉, 饶志粒, 等. 逍遥散对LPS所致大鼠神经损伤的保护作用机制[J]. 中国实验方剂学杂志, 2019,25(5):50-56. DOI： 10.13422/j.cnki.syfjx.20190536.

Bo-yu SHI, Rong LIU, Zhi-li RAO, et al. Neuroprotective Effect and Mechanism of Xiaoyaosan on Lipopolysaccharide-induced Nerve Injury in Rat[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(5): 50-56. DOI： 10.13422/j.cnki.syfjx.20190536.

摘要

目的：

探讨逍遥散对脂多糖(LPS)所致大鼠神经损伤的保护作用，探讨其机制。

方法：

56只SD大鼠随机分为空白组，假手术组，模型组，阿米替林组(10mg·kg

－1

)，氟西汀组(10mg·kg

－1

)，逍遥散高、低剂量组(30

15g·kg

－1

)，采用侧脑室注射LPS诱导建立神经损伤大鼠模型，连续预防灌胃给药14d，酶联免疫吸附测定(ELISA)检测大鼠血清脑源性神经营养因子(BDNF)和

-神经生长因子(

-NGF)水平，实时荧光定量聚合酶链式反应(Real-time PCR)与蛋白免疫印迹法(Western blot)检测大鼠海马和皮层部位BDNF，神经生长因子(NGF)，原肌球蛋白受体激酶B(TrkB)，原肌球蛋白受体激酶A(TrkA)，cAMP反应元件结合蛋白(CREB)，突触后密度蛋白95(PSD95)，突触小泡蛋白(SYP)mRNA或蛋白表达水平。

结果：

与空白组比较，模型组大鼠血清BDNF

-NGF含量显著下降(

0.01)，皮层、海马BDNF

NGF

TrkB

TrkA

CREB mRNA明显下调(

0.05，

0.01)，BDNF

TrkB

CREB，磷酸化cAMP反应元件结合蛋白(p-CREB)，PSD95，SYP蛋白表达水平明显下调(

0.05，

0.01)；与模型组比较，逍遥散高、低剂量组大鼠血清BDNF

-NGF含量明显升高(

0.05，

0.01)，皮层、海马BDNF

NGF

TrkB

TrkA

CREB mRNA表达水平明显上调(

0.05，

0.01)，BDNF

TrkB

CREB

p-CREB

PSD95，SYP蛋白表达水平明显上调(

0.05，

0.01)。

结论：

逍遥散对侧脑室注射LPS诱导的大鼠神经损伤有一定保护作用，作用发挥与活化BDNF/NGF-TrkB/TrkA-CREB通路及上调突触蛋白表达有关。

Abstract

Objective:

To investigate the effect and mechanism of Xiaoyaosan on lipopolysaccharide(LPS)-induced nerve injury.

Method:

The 56 rats were randomly divided into control group

sham group

model group

amitriptyline group (10mg·kg

-1

)

fluoxetine group (10mg·kg

-1

)

Xiaoyaosan group high and low-dose (30

15g·kg

-1

). The nerve injury model rat were established by LPS injection into lateral ventride

rats were administrated for 14 days by gavage. The levels of brain-derived neurotrophic factor (BDNF) and

-nerve growth factor (

-NGF) in serum were detected by enzyme linked immunosorbent assay(ELISA)

and the expressions of BDNF

nerve growth factor (NGF)

tropomyosin receptor kinase B (TrkB)

tropomyosin receptor kinase A (TrkA)

cAMP response element-binding protein (CREB) mRNA in hippocampus and cortex were detected by Real-time PCR.Protoin expression of BDNF

TrkB

CREB

p-CREB

postsynaptic density protein 95 (PSD95)

synaptophysin (SYP) in hippocampus and cortex were detected by Western blot.

Result:

Compared with control group

LPS decreased the level of BDNF and

-NGF in serum(

0.01)

reduced the expression of BDNF

NGF

TrkB

TrkA

CREB mRNA and the expression of BDNF

TrkB

CREB

Phospho-CREB (p-CREB)

PSD95

SYP in hippocampus and cortex(

0.05

0.01). Compared with model group

levels of BDNF and

-NGF in serum in Xiaoyaosan high and low-dose group were increased significantly (

0.05

0.01)

and expressions of BDNF

NGF

TrkB

TrkA

CREB

PSD95

SYP in hippocampus and cortex were increased significantly (

0.05

0.01).

Conclusion:

Xiaoyaosan has a certain antagonistic effect on LPS inducednerve injury

which suggests that the effect is related to activate BDNF/NGF-TrkB/TrkA-CREB pathway and upregulated the expression of synaptic protein.

关键词

Keywords

references

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