坏死性小肠结肠炎对新生小鼠脑损伤及其程度的影响

王雪; 邹谋; 张绍卿; 刘兰; 杜敏; 徐颖

doi:10.16016/j.1000-5404.202103125

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坏死性小肠结肠炎对新生小鼠脑损伤及其程度的影响

基础医学 | 更新时间：2026-01-09

- 坏死性小肠结肠炎对新生小鼠脑损伤及其程度的影响
- Effects of necrotizing enterocolitis on brain injury and its severity in neonatal mice
- 第三军医大学学报 2021年43卷第17期页码：1634-1641
- 作者机构：
- 作者简介：
- 基金信息：
  
  重庆市技术创新与应用示范（社会民生类）一般项目(cstc2018jscx-msybX0104)
- DOI：10.16016/j.1000-5404.202103125
  中图分类号：
- 收稿：2021-03-14，
  
  纸质出版：2021-09-15
- 稿件说明：
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王雪, 邹谋, 张绍卿, 等. 坏死性小肠结肠炎对新生小鼠脑损伤及其程度的影响[J]. 第三军医大学学报, 2021,43(17):1634-1641.

Xue WANG, Mou ZOU, Shaoqing ZHANG, et al. Effects of necrotizing enterocolitis on brain injury and its severity in neonatal mice[J]. Journal of Third Military Medical University, 2021, 43(17): 1634-1641.
王雪, 邹谋, 张绍卿, 等. 坏死性小肠结肠炎对新生小鼠脑损伤及其程度的影响[J]. 第三军医大学学报, 2021,43(17):1634-1641. DOI： 10.16016/j.1000-5404.202103125.

Xue WANG, Mou ZOU, Shaoqing ZHANG, et al. Effects of necrotizing enterocolitis on brain injury and its severity in neonatal mice[J]. Journal of Third Military Medical University, 2021, 43(17): 1634-1641. DOI： 10.16016/j.1000-5404.202103125.

摘要

目的

探讨不同程度坏死性小肠结肠炎（necrotizing enterocolitis，NEC）对新生小鼠脑损伤的影响。

方法

将60只5日龄C57BL/6小鼠随机分为对照组（CON组，

=20）和坏死性小肠结肠炎组（NEC组，

=40）。CON组与母鼠同笼，母乳喂养；NEC组饲养在保育箱，采用配方奶喂养+缺氧+口服脂多糖（LPS）诱导坏死性小肠结肠炎小鼠模型，建模4 d后处死所有小鼠。建模过程中记录小鼠每日体质量并观察一般情况；HE染色观察肠道组织的病理学改变。根据回盲部肠道损伤评分将NEC组分为轻度NEC组（

=12）和重度NEC组（

=12）；Nissl染色观察相应脑组织的病理学变化，并将肠道损伤程度和神经细胞的数量做相关性分析。RT-qPCR检测脑组织中炎症因子IL-1β、IL-6和TNF-α mRNA的表达水平；酶联免疫吸附法（ELISA）检测脑组织炎症因子IL-1β、IL-6和TNF-α蛋白的表达水平；免疫荧光检测活化的小胶质细胞和星形胶质细胞的数量。

结果

与CON组相比，NEC组小鼠活动度降低，体质量明显减轻（3.84±1.25

1.76±0.26

g，

0.05），肠道损伤严重，且在海马CA1区，轻、重度NEC组的神经细胞数量减少（125.83±6.40

103.83±7.93、75.50±8.87，

0.05），重度NEC组较轻度NEC组减少更多（

0.05）；相关性分析显示：神经细胞数量与肠道损伤的严重程度呈负相关（

=－0.943，

0.001）。与CON组相比，NEC组脑组织炎症因子IL-1β、IL-6和TNF-ɑ的表达水平均升高（

0.05），活化的小胶质细胞和星形胶质细胞也明显增多（

0.05），并且重度NEC组较轻度NEC组升高更明显（

0.05）。

结论

坏死性小肠结肠炎可导致新生小鼠发生急性脑损伤，其损伤程度与肠道损伤的严重程度相关，可能与神经炎症的增加有关。

Abstract

Objective

To investigate the effect of necrotizing enterocolitis (NEC) at different severities on brain injury in neonatal mice.

Methods

Sixty 5-day old C57BL/6 mice were randomly divided into control group (CON group

=20) and NEC group (

=40). The CON group was breeding with female mice and breast-fed. The NEC group was fed in an incubator

and induced by formula gavage feeding+hypoxia+oral lipopolysaccharide (LPS) to establish the model of NEC. In 4 d after NEC modeling

all pups were sacrificed by cervical decapitation. Their body weight was measured and general conditions were observed. HE staining was used to observe the pathological changes of intestinal tissue. NEC group was divided into mild NEC subgroup and severe NEC subgroup according to the intestinal injury score of ileocecus. Nissl staining was employed to further observe the pathological changes of the corresponding brain tissue. The correlation between the severity of intestinal injury and the number of nerve cells was analyzed with Pearson analysis. The mRNA levels of the inflammatory factors interleukin-1β (IL-1β)

IL-6 and tumor necrosis factor-α (TNF-α) in brain tissues were measured with quantitative real-time PCR (RT-qPCR). Enzyme-linked immunosorbent assay (ELISA) was adopted to detect the protein contents of IL-1β

IL-6 and

TNF-α in brain tissues. Immunofluorescence assay was conducted to detect the number of activated microglia and astrocytes in the hippocampus.

Results

Compared with CON group

the NEC group had decreased activities and lower body weight (3.84±1.25

1.76±0.26 g

0.05)

and serious intestinal damage. The number of nerve cells in the hippocampus were significantly reduced in the NEC group than the CON group (

0.05)

so was in the severe NEC subgroup than that the mild NEC subgroup (

0.05). Correlation analysis showed that the pathological changes of brain were negatively correlated with the severity of intestinal injury (

=- 0.943

0.001). When compared with the CON group

the mRNA and protein levels of IL-1β

IL-6 and TNF-α in brain tissues were significantly elevated (

0.05)

and the numbers of activated microglia and astrocytes were also significantly increased in the NEC group (

0.05)

especially in the severe NEC subgroup (

0.05).

Conclusion

NEC can lead to acute brain injury in neonatal mice

and the severity of damage is related to the severity of intestinal injury

which may be related to the increase of neuroinflammation.

关键词

Keywords

references

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