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间质基质细胞抑制低氧缺血性脑损伤诱导的海马神经元自噬应激:内源性 IL-6 分泌的可能作用。

Mesenchymal Stromal Cells Suppress Hippocampal Neuron Autophagy Stress Induced by Hypoxic-Ischemic Brain Damage: The Possible Role of Endogenous IL-6 Secretion.

机构信息

Children's Nutrition Research Center, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.

Chongqing Key Laboratory of Child Nutrition and Health, Chongqing 400014, China.

出版信息

Neural Plast. 2020 Aug 28;2020:8822579. doi: 10.1155/2020/8822579. eCollection 2020.

Abstract

BACKGROUND

Increasing evidence has revealed that mesenchymal stromal cell (MSC) transplantation alleviates hypoxic-ischemic brain damage (HIBD) induced neurological impairments via immunomodulating astrocyte antiapoptosis effects. However, it remains unclear whether MSCs regulate neuron autophagy following HIBD.

RESULTS

In the present study, MSC transplantation effectively ameliorated learning-memory function and suppressed stress-induced hippocampal neuron autophagy in HIBD rats. Moreover, the suppressive effects of MSCs on autophagy were significantly weakened following endogenous IL-6 silencing in MSCs. Suppressing IL-6 expression also significantly increased p-AMPK protein expression and decreased p-mTOR protein expression in injured hippocampal neurons.

CONCLUSION

Endogenous IL-6 in MSCs may reduce autophagy in hippocampal neurons partly through the AMPK/mTOR pathway.

摘要

背景

越来越多的证据表明,间充质基质细胞(MSC)移植通过免疫调节星形胶质细胞抗细胞凋亡作用来减轻缺氧缺血性脑损伤(HIBD)引起的神经损伤。然而,目前尚不清楚 MSC 是否会调节 HIBD 后神经元的自噬。

结果

在本研究中,MSC 移植有效改善了 HIBD 大鼠的学习记忆功能,并抑制了应激诱导的海马神经元自噬。此外,在 MSC 中内源性沉默 IL-6 后,MSC 对自噬的抑制作用明显减弱。抑制 IL-6 的表达也显著增加了损伤海马神经元中 p-AMPK 蛋白的表达,降低了 p-mTOR 蛋白的表达。

结论

MSC 中的内源性 IL-6 可能通过 AMPK/mTOR 通路部分减少海马神经元中的自噬。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f847/7474748/d91639f2a741/NP2020-8822579.001.jpg

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