二甲双胍减轻脂多糖诱导的脓毒症小鼠脑损伤

田径; 董艳; 刘刚; 张力; 唐玲

doi:10.16016/j.1000-5404.201902108

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二甲双胍减轻脂多糖诱导的脓毒症小鼠脑损伤

基础医学 | 更新时间：2026-01-09

- 二甲双胍减轻脂多糖诱导的脓毒症小鼠脑损伤
- Metformin attenuates brain damage in mouse model of lipopolysaccharide-induced sepsis
- 第三军医大学学报 2019年41卷第15期页码：1423-1430
- 作者机构：
- 作者简介：
- 基金信息：
  
  重庆市教委科学技术研究项目(2015X9517)
- DOI：10.16016/j.1000-5404.201902108
  中图分类号：
- 收稿：2019-02-24，
  
  纸质出版：2019-08-15
- 稿件说明：
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田径, 董艳, 刘刚, 等. 二甲双胍减轻脂多糖诱导的脓毒症小鼠脑损伤[J]. 第三军医大学学报, 2019,41(15):1423-1430.

Jing TIAN, Yan DONG, Gang LIU, et al. Metformin attenuates brain damage in mouse model of lipopolysaccharide-induced sepsis[J]. Journal of Third Military Medical University, 2019, 41(15): 1423-1430.
田径, 董艳, 刘刚, 等. 二甲双胍减轻脂多糖诱导的脓毒症小鼠脑损伤[J]. 第三军医大学学报, 2019,41(15):1423-1430. DOI： 10.16016/j.1000-5404.201902108.

Jing TIAN, Yan DONG, Gang LIU, et al. Metformin attenuates brain damage in mouse model of lipopolysaccharide-induced sepsis[J]. Journal of Third Military Medical University, 2019, 41(15): 1423-1430. DOI： 10.16016/j.1000-5404.201902108.

摘要

Abstract

Objective

To explore the mitigative effect of metformin on brain damage in mice with lipopolysaccharide (LPS)-induced sepsis.

Methods

A total of 104 male BALB/c mice were randomly divided into 4 groups (

=26)

that is

control

metformin

LPS and LPS+metformin group. LPS of 20 mg/kg was intraperitoneally injected to mice to induce sepsis-like systemic inflammation

and metformin (400 mg/kg) was given intraperitoneally in 0.5 h before LPS injection. Serum and brain

samples were harvested 18 h after LPS administration. HE staining was performed for the histological observation in the brain tissues. Evans blue staining was used to evaluate the permeability of the blood-brain barrier (BBB). The activity of Caspase-3

content of malondialdehyde (MDA)

and levels of IL-6

TNF-α and myeloperoxidase (MPO) in brain samples

and the levels of neuron-specific enolase (NSE) and soluble protein100-β (S100-β) in serum were determined with corresponding reagent testing kits.

Results

In the morphological observation on hippocampal CA1 and CA3 regions and cerebral cortex

the results indicated that LPS exposure induced large quantities of widespreading degenerative neurons

and these abnormalities were attenuated in mice receiving metformin administration. The elevated Evans blue content in the brain from LPS-insulted mice was decreased by metformin (

0.05). Treatment with metformin suppressed LPS-induced elevation of NSE and S100-β in the serum (

0.05). The activity of Caspase-3 was significantly higher in LPS group than the control group (

0.01)

while the activity of Caspase-3 in LPS+metformin group was lower than in LPS group (

0.05)

which was higher than that in control group and metformin group (

0.05). Metformin treatment decreased the contents of IL-6

TNF-α and MPO in the brain tissue from LPS-insulted mice (

0.05). In addition

metformin treatment inhibited LPS-induced increase of MDA in brain tissue (

0.01).

Conclusion

Metformin alleviates LPS-induced brain damage

which may associated with protection of BBB

inhibition of apoptosis

suppressed inflammatory response and attenuated oxidative stress. Metformin might have therapeutic value in sepsis-associated brain damage.

关键词

Keywords

references

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