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热休克蛋白 70 通过激活 NF-κB 通路缓解脊髓损伤。

HSP70 alleviates spinal cord injury by activating the NF-kB pathway.

机构信息

Shaanxi Provincial People's Hospital, Xi'an, China.

Department of Anesthesiology, Shaanxi Provincial Cancer Hospital, Xi'an, China.

出版信息

J Musculoskelet Neuronal Interact. 2021 Dec 1;21(4):542-549.

Abstract

OBJECTIVES

Spinal cord injury (SCI) is an acute traumatic lesion of neurons in the spinal cord which has a high prevalence in the world, and has no effective surgical treatment. HSP70 is a molecular chaperone protein, serves a protective role in several different models of nervous system injury. The aim of the present study was to investigate the anti-inflammatory role of HSP70 in spinal cord injury and explore its mechanism.

METHODS

In vivo and in vitro models were constructed to mimic SCI. The Basso Mouse Scale (BMS) was applied to assess SCI degrees of the mouse model. Immunofluorescence (IF) was used for visualizing HSP70 and Iba1 in the spinal cord. Western blot assay was employed to quantify HSP70 and p65, and ELISA was for IL-1β and TNF-α.

RESULTS

The results showed that HSP70 expression decreased after SCI. HSP70 and Iba1 showed a decrease of co-localization in SCI mice. Further studies revealed that p65 was upregulated during the process of SCI. Overexpression of HSP70 inhibited the expression of p65 both in vitro and in vivo, and promoted the recovery of SCI mice.

CONCLUSIONS

HSP70 was involved in the pathological process of spinal cord injury, HSP70 alleviated the spinal cord injury via inhibiting NF-κB signaling pathway.

摘要

目的

脊髓损伤(SCI)是一种脊髓神经元的急性创伤性病变,在世界范围内发病率很高,目前尚无有效的手术治疗方法。热休克蛋白 70(HSP70)是一种分子伴侣蛋白,在几种不同的神经系统损伤模型中发挥保护作用。本研究旨在探讨 HSP70 在脊髓损伤中的抗炎作用及其机制。

方法

构建体内和体外模型模拟脊髓损伤。采用 Basso 小鼠运动评分(BMS)评估小鼠模型的 SCI 程度。免疫荧光(IF)用于观察脊髓中 HSP70 和 Iba1 的表达。Western blot 用于定量 HSP70 和 p65 的表达,ELISA 用于检测 IL-1β 和 TNF-α 的水平。

结果

结果显示,SCI 后 HSP70 表达降低。HSP70 和 Iba1 在 SCI 小鼠中的共定位减少。进一步的研究表明,p65 在 SCI 过程中上调。HSP70 的过表达在体外和体内均抑制了 p65 的表达,并促进了 SCI 小鼠的恢复。

结论

HSP70 参与了脊髓损伤的病理过程,HSP70 通过抑制 NF-κB 信号通路缓解脊髓损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d422/8672413/eea9092b2f6d/JMNI-21-542-g001.jpg

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