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自主运动和益赛普对于创伤性脑损伤小鼠的神经保护作用

甘甜甜¹, 廖琪¹, 汪际慧¹, 范志恒¹, 曹健¹, 潘慧炬¹, 娄高峰², 董雪芬¹, 欧阳玮^1,*

¹浙江师范大学体育与健康科学学院，金华 321004；²浙江金华广福医院内分泌科，金华 321004

摘要

运动在创伤性脑损伤(traumatic brain injury, TBI)后的神经保护作用机制仍有待揭示。目前也缺乏针对TBI的有效治疗手段。本研究旨在考察自主运动和注射益赛普(Yisaipu，TNFR-IgG融合蛋白，TNF抑制剂)联用方式对TBI模型小鼠的影响。雄性C57BL/6J小鼠被随机分为对照组和自主运动组，然后观察6周预防性预自主运动(prophylactic preconditioning exercise, PE)和/或TBI 后注射Yisaipu 对中度TBI小鼠的影响。 结果显示，与单一干预措施比较，PE和Yisaipu的联合干预能更有效减少TBI小鼠的感觉运动和步态功能障碍。同时，这些功能改善伴随着外周血清TNF-α水平下降、系统性炎症减轻、脑内自噬流途径增强和皮层损伤灶体积缩小。鉴于上述神经保护作用，诸如运动和TNF抑制剂联用方式可能是促进TBI患者功能恢复的有效策略，值得进一步研究。

关键词： 自主运动; 益赛普; 创伤性脑损伤; 神经功能缺陷; 运动障碍

Neuroprotective effects of voluntary exercise and Yisaipu after traumatic brain injury in mice

GAN Tian-Tian¹, LIAO Qi¹, WANG Ji-Hui¹, FAN Zhi-Heng¹, CAO Jian¹, PAN Hui-Ju¹, LOU Gao-Feng², DONG Xue-Fen¹, OUYANG Wei^1,*

¹College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua 321004, China；²Department of Endocrinology, Zhejiang Jinhua Guangfu Hospital, Jinhua 321004, China

Abstract

The mechanisms underlying exercise-induced neuroprotective effects after traumatic brain injury (TBI) remained elusive, and there is a lack of effective treatments for TBI. In this study, we investigated the effects of an integrative approach of exercise and Yisaipu (TNFR-IgG fusion protein, TNF inhibitor) in a mouse TBI model. Male C57BL/6J mice were randomly assigned to a sedentary group or a group that followed a voluntary exercise regimen. The effects of 6-week prophylactic preconditioning exercise (PE) alone or in combination with post-TBI Yisaipu treatment on moderate TBI associated deficits were examined. The results showed that combined treatments of PE and post-TBI Yisaipu were superior to single treatments on reducing sensorimotor and gait dysfunctions in mice. These functional improvements were accompanied by reduced systemic inflammation largely via decreased serum TNF-α, boosted autophagic flux, and mitigated lesion volume after TBI. Given these neuroprotective effects, composite approaches such as a combination of exercise and TNF inhibitor may be a promising strategy for facilitating functional recovery from TBI and are worth further investigation.  

Key words: voluntary exercise; Yisaipu; traumatic brain injury; neurological deficits; motor disability

收稿日期：　　录用日期：

通讯作者：欧阳玮　　E-mail: wouyang@zjnu.cn

DOI: 10.13294/j.aps.2022.0037

引用本文：

甘甜甜, 廖琪, 汪际慧, 范志恒, 曹健, 潘慧炬, 娄高峰, 董雪芬, 欧阳玮. 自主运动和益赛普对于创伤性脑损伤小鼠的神经保护作用[J]. 生理学报 2022; 74 (3): 333-352.

GAN Tian-Tian, LIAO Qi, WANG Ji-Hui, FAN Zhi-Heng, CAO Jian, PAN Hui-Ju, LOU Gao-Feng, DONG Xue-Fen, OUYANG Wei. Neuroprotective effects of voluntary exercise and Yisaipu after traumatic brain injury in mice. Acta Physiol Sin 2022; 74 (3): 333-352