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  

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

作　　者：甘甜甜 廖琪 汪际慧[1] 范志恒 曹健 潘慧炬[1] 娄高峰 董雪芬[1] 欧阳玮[1] GAN Tian-Tian;LIAO Qi;WANG Ji-Hui;FAN Zhi-Heng;CAO Jian;PAN Hui-Ju;LOU Gao-Feng;DONG Xue-Fen;OUYANG Wei(College of Physical Education and Health Sciences,Zhejiang Normal University,Jinhua 321004,China;Department of Endocrinology,Zhejiang Jinhua Guangfu Hospital,Jinhua 321004,China)

机构地区：[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

出　　处：《生理学报》2022年第3期333-352,共20页Acta Physiologica Sinica

基　　金：supported by the Natural Science Foundation of Zhejiang Province,China(No.LY20H150001);the Key Social Development Foundation of Jinhua Municipality(No.2020-3-071);the National Innovation and Entrepreneurship Training Program for College Students(No.201710345005)。

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。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.

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 

分 类 号：R651.15[医药卫生—外科学]