丰富环境通过转录因子EB介导自噬对缺血性脑卒中大鼠神经功能损伤的影响

doi:10.13481/j.1671-587X.20260112

Abstract

Abstract:

Objective To discuss the impact of an enriched environment （EE） on ischemic stroke （IS） injury， and to preliminarily clarify the role of transcription factor EB （TFEB） protein in this process as well as the relationship between EE and inflammatory response and oxidative stress response. Methods Forty?eight SD rats were randomly divided into control group， cerebral ischemia （IS） group， IS+EE group， and IS+EE+chloroquine （CQ） group （IS+EE+CQ group）， with 12 rats in each group in experiment Ⅰ. Another 16 rats were randomly divided into IS+EE+sh-NC group and IS+EE+sh-TFEB group， with 8 rats in each group in experiment Ⅱ. Before model establishment， the rats in IS+EE+sh-TFEB group were injected with TFEB shRNA into the cerebral ventricle to silence TFEB expression in brain tissue. Except for control group， the IS model was established in the rats in the other groups using the Longa suture?occlusion method. The modified neurological severity score （mNSS） was used to evaluate the neurological function injury of the rats in various groups； triphenyltetrazolium chloride （TTC） staining was used to detect the percentages of cerebral infarction area of the rats in various groups； kits were used to detect the levels of inflammatory cytokines and oxidative stress factors of the rats in various groups； Western blotting method was used to detect the expression levels of autophagy-related proteins of the rats in various groups. Results Compared with control group， the mNSS score of the rats in IS group was increased （P<0.05）， the levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and malondialdehyde （MDA） in the brain tissue in ischemic penumbra region were increased （P<0.05）， the activity of superoxide dismutase （SOD） was decreased （P<0.05）， and the expression levels of TFEB and Beclin-1 proteins and the ratio of microtubule-associated protein 1 light chain 3 （LC3）-Ⅱ/LC3-Ⅰ were decreased （P<0.05）. Compared with IS group， the mNSS score and the percentage of cerebral infarction area of the rats in IS+EE group were decreased （P<0.05）， the levels of IL-6， IL-1β， TNF-α， and MDA in the brain tissue in ischemic penumbra region were decreased （P<0.05）， the activity of SOD was increased （P<0.05）， and the expression levels of TFEB and Beclin-1 proteins and the ratio of LC3-Ⅱ/LC3-Ⅰ were increased （P<0.05）. Compared with IS+EE group， the mNSS score and the percentage of cerebral infarction area of the rats in IS+EE+CQ group were increased （P<0.05）， the levels of IL-6， IL-1β， TNF-α， and MDA in the brain tissue in ischemic penumbra region were increased （P<0.05）， the activity of SOD was decreased （P<0.05）， and the expression levels of TFEB and Beclin-1 proteins and the ratio of LC3-Ⅱ/LC3-Ⅰ were decreased （P<0.05）. Compared with IS+EE+sh?NC group， the mNSS score of the rats in IS+EE+sh-TFEB group was decreased （P<0.05）， the percentage of cerebral infarction area was increased （P<0.05）， and the expression levels of TFEB and Beclin-1 proteins and the ratio of LC3-Ⅱ/LC3-Ⅰ in the brain tissue in ischemic penumbra region were decreased （P<0.05）. Conclusion EE has a significant ameliorative effect on neurological function injury in the IS rats， and its mechanism may be related to EE inducing autophagy by increasing TFEB protein expression， thereby alleviating neuroinflammation and oxidative stress in the ischemic brain region.

Key words: Enriched environment, Inflammation, Autophagy, Transcription factor EB, Ischemic stroke

CLC Number:

R743

Huiyan ZHU,Min CHEN,Jinxian LI,Chunli LI. Effect of enriched environment on neurofunctional damage in rats with ischemic stroke via transcription factor EB-mediated autophagy[J].Journal of Jilin University(Medicine Edition), 2026, 52(1): 116-124.

Figures/Tables 6

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References 21

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Group	Neurological function score			Balance duration in motor function （t/s）
Group	1st day	3rd day	7th day	1st day	3rd day	7th day
Control	0.17±0.39	0.08±0.29	0.00±0.00	142.00±26.78	147.67±22.01	138.33±25.70
IS	10.17±2.69^*	8.33±2.19^*	7.92±2.87^*	16.67±11.88^*	21.83±15.75^*	24.00±16.81^*
IS+EE	9.83±1.95	6.25±1.42^△	5.08±1.88^△	17.83±15.47	36.25±19.47	55.83±28.84^△
IS+EE+CQ	9.67±2.42	9.08±1.38^#	8.92±1.93^#	20.67±14.92	19.33±12.60	22.33±13.25^#

Group	IL-6 [w_B/(ng·g^-1)]	IL-1β [w_B/(ng·g^-1)]	TNF-α [w_B/(ng·g^-1)]	MDA [m_B/(μmol·g^-1)]	SOD [λ_B/(U·mg^-1)]
Control	22.21±6.06	21.84±7.84	35.82±10.32	2.51±0.91	162.99±27.96
IS	181.85±73.12^*	173.30±85.38^*	297.51±129.33^*	52.86±18.40^*	28.39±9.90^*
IS+EE	55.71±19.47^△	32.11±7.38^△	55.29±16.91^△	10.05±2.22^△	102.24±14.95^△
IS+EE+CQ	154.50±40.35^#	190.62±63.93^#	290.34±112.11^#	45.24±14.03^#	27.61±10.88^#

Effect of enriched environment on neurofunctional damage in rats with ischemic stroke via transcription factor EB-mediated autophagy

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