Effect of TGF-β1 on intermittent hypoxia induced autophagy in hippocampal neurons

Xin WANG; Zhili LIU; Yinpei HUANG; Dan YU; Bing LI

doi:10.16016/j.1000-5404.202101181

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Effect of TGF-β1 on intermittent hypoxia induced autophagy in hippocampal neurons

Neurosciences | 更新时间：2026-01-09

- Effect of TGF-β1 on intermittent hypoxia induced autophagy in hippocampal neurons
- Journal of Third Military Medical University Vol. 43, Issue 14, Pages: 1312-1318(2021)
- 作者机构：
  
  400016 重庆，重庆医科大学附属第一医院耳鼻咽喉头颈外科
- 作者简介：
- 基金信息：
  
  the General Program of Chongqing Science and Technology Commission(CSTC2016shmszx130035)
- DOI：10.16016/j.1000-5404.202101181
  CLC： R338.1;R363.25;R364.4
- Received：22 January 2021，
  
  Revised：2021-03-23，
  
  Published：30 July 2021
- 稿件说明：
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Xin WANG, Zhili LIU, Yinpei HUANG, et al. Effect of TGF-β1 on intermittent hypoxia induced autophagy in hippocampal neurons[J]. Journal of Third Military Medical University, 2021, 43(14): 1312-1318.
DOI：

Xin WANG, Zhili LIU, Yinpei HUANG, et al. Effect of TGF-β1 on intermittent hypoxia induced autophagy in hippocampal neurons[J]. Journal of Third Military Medical University, 2021, 43(14): 1312-1318. DOI： 10.16016/j.1000-5404.202101181.

摘要

目的

探讨TGF-β1对间歇性缺氧诱导海马神经元自噬的影响。

方法

体内实验: 将12只SD大鼠按完全随机分组方法分为对照组(N组)和间歇性缺氧组(IH组)，Morris水迷宫评估大鼠认知功能；透射电镜、免疫组织化学观察神经元的自噬改变；Western blot检测LC3、P62及TGF-β1的表达。体外实验: 将小鼠海马神经元细胞系HT22细胞分为对照组(N组)、间歇性缺氧组(IH组)、间歇性缺氧+TGF-β1组(IH+TGF-β1组)和间歇性缺氧+SB431542组(IH+SB431542组)，Western blot检测TGF-β1、LC3和P62的表达。

结果

与N组相比，IH组Morris水迷宫实验平均逃逸潜伏期延长(

0.05)，目标象限停留时间延长(

0.05)；电镜下自噬小体增多，免疫组织化学LC3染色增加；体内体外实验中Western blot结果显示LC3-Ⅱ/LC3-Ⅰ、P62表达上调(

0.05)，TGF-β1表达下调(

0.05)；与IH组相比，IH+TGF-β1组TGF-β1表达上调(

0.05)，LC3-Ⅱ/LC3-Ⅰ、P62表达降低(

0.05)，IH+SB431542组LC3-Ⅱ/LC3-Ⅰ表达增加(

0.05)。

结论

间歇性缺氧导致大鼠认知功能障碍，可能与神经元自噬累积有关，TGF-β1可以减轻间歇性缺氧诱导的自噬增多。

Abstract

Objective

To investigate the effect of TGF-β1 on autophagy in hippocampal neurons induced by intermittent hypoxia.

Methods

In vivo

experiment: Twelve SD rats were randomly divided as control group (N group) and intermittent hypoxia group (IH group); Their cognitive function was assessed by Morris water maze; Neuronal autophagy was observed by transmission electron microscopy and immunohistochemical assay; The expression of LC3

P62 and TGF-β1 in the hippocampus was detected by Western blotting.

In vitro

experiment: the mouse hippocampal neuron cell line (HT22 cells) was divided as control group (N group)

intermittent hypoxia group (IH group)

intermittent hypoxia+TGF-β1 group (IH+TGF-β1 group) and intermittent hypoxia+SB431542 group (IH+SB431542 group)

the expression of TGF-β1

LC3 and P62 was detected by Western blotting.

Results

Compared with the N group

the average escape latency and the residence time in the target quadrant were both prolonged in the IH group (

0.05). Besides

the number of autophagosomes was increased under electron microscope and the stained intensity of LC3 was enhanced in immunohistochemical assay. Western blotting indicated that the expression of LC3-Ⅱ/LC3-Ⅰ and P62 was up-regulated (

0.05)

while that of TGF-β1 was down-regulated (

0.05) in the

in vitro

and

in vivo

experiments. Compared with the IH group

the protein level of TGF-β1 was up-regulated

while that of LC3-Ⅱ/LC3-Ⅰ and P62 was decreased (

0.05) in the IH+TGF-β1 group (

0.05); The expression of LC3-Ⅱ/LC3-Ⅰ was increased in the IH+SB431542 group (

0.05).

Conclusion

Intermittent hypoxia causes cognitive dysfunction in rats

which is probably related to the accumulation of neuronal autophagy. TGF-β1 attenuates the increase of neuronal autophagy induced by intermittent hypoxia.

关键词

Keywords

references

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