摘要
目的 研究脑神经炎症状态与运动疲劳之间的关联,并从脑能量代谢角度探讨其可能机制。方法 实验采用雄性C57BL/6J小鼠。(1)小鼠分为溶剂对照和脂多糖(LPS)组(每只小鼠2.5μg)、米诺环素组(每只小鼠12μg)、AZD3965组(每只小鼠50 nmol)或4-CIN组(每只小鼠40 nmol),每组12只,LPS侧脑室注射(icv)给药12 h,米诺环素、AZD3965和4-CIN组分别icv给药后30 min进行小鼠转棒实验,测定小鼠在棒时间。(2)小鼠分为溶剂对照和米诺环素3个剂量组(每只小鼠3,6和12μg),每组12只,米诺环素icv给药后30 min进行小鼠跑台实验,测定小鼠运动持续时间和运动距离;或分为溶剂对照和米诺环素组(每只小鼠12μg),每组12只,米诺环素icv给药后30 min进行小鼠负重游泳实验,测定小鼠游泳持续时间。(3)小鼠分为溶剂对照、LPS(每只小鼠2.5μg)和LPS+米诺环素组(每只小鼠2.5μg+12μg),每组12只,LPS组为LPS icv给药后12 h、LPS+米诺环素组为icv给予LPS后12 h再icv给予米诺环素后30 min进行小鼠跑台实验和负重游泳实验,或处死取大脑运动皮质,逆转录实时定量PCR检测大脑运动皮质中白细胞介素1β(IL-1β)、IL-6和肿瘤坏死因子α(TNF-α)及单羧酸转运体1(MCT-1),MCT-2和MCT-4 mRNA表达水平。(4)小鼠分为溶剂对照和AZD3965 3个剂量组(每只小鼠12.5,25和50 nmol)、4-CIN 3个剂量组(每只小鼠10,20和40 nmol)、AZD3965组(每只小鼠50 nmol)或4-CIN 1组(每只小鼠40 nmol),每组12只,icv给予AZD3965和4-CIN后30 min进行小鼠跑台实验和负重游泳实验。结果 (1)与溶剂对照组相比,LPS、米诺环素、AZD3965和4-CIN对小鼠在棒时间均无影响,表明它们均不影响小鼠运动协调性。(2)与溶剂对照组比较,米诺环素(每只小鼠12μg)显著增加小鼠跑台运动持续时间、运动距离和小鼠负重游泳持续时间(P<0.01)。(3) LPS(每只小鼠2.5μg)显著降低小鼠跑台运动持续时间、运动距离和小鼠负重游泳持续时间(P<0.
OBJECTIVE To investigate the correlation between neuroinflammation and exercise fatigue and to study the possible mechanism from the perspective of brain energy metabolism.METHODS Male C57BL/6J mice were used in this study.①To investigate the effect of drug administration on exercise fatigue of mice,the mice were divided into the vehicle group,lipopolysaccharides(LPS,2.5μg per mouse)group or minocycline(12μg per mouse)or AZD3965(50 nmol per mouse)or 4-CIN(40 nmol per mouse)groups.The rotate bar test was used to measure the time mice spent on the rotating bar 12 h after the mice were intracerebroventricularly injected(icv)with LPS,or 30 min after icv with minocycline,AZD3965 and 4-CIN,respectively.②To investigate the effect of reducing neuroinflammation on exercise fatigue,the mice were divided into vehicle and 3 different doses of minocycline(3,6 and 12μg per mouse)groups,or vehicle and a single dose of minocycline(12μg per mouse)groups.The running duration and distance covered by mice on the treadmill were determined with the treadmill test.The load swimming test was conducted 30 min after the mice were icv with minocycline.③To investigate the effect of LPS on exercise fatigue and the reversal effect of minocycline on LPS′s action,the mice were divided into the vehicle,LPS(2.5μg per mouse)and LPS+minocycline(2.5μg+12μg per mouse)groups.The mice of the LPS+minocycline group were icv with minocycline 12 h after icv LPS.The treadmill test and load swimming test were used to assess the endurance exercise fatigue of the mice or the motor cortex was collected after the mice were sacrificed 12 h after they were icv with LPS or 30 min after icv with minocycline.The mRNA expression levels of interleukin-1β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α),and monocarboxylate transporters-1(MCT-1),MCT-2 and MCT-4 in the motor cortex were detected with reverse transcription and real-time quantitative PCR.④To investigate the effect of AZD3965 and 4-CIN on exercise fatigue,the mice were divided into the veh
作者
曹奕炜
宋睿
吴宁
李锦
CAO Yi-wei;SONG Rui;WU Ning;LI Jin(Graduate School,Nanjing University of Chinese Medicine,Nanjing 210023,China;Beijing Key Laboratory of Neuropsychopharmacology,State Key Laboratory of Toxicology and Medical Counter-measure,Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Beijing 100850,China)
出处
《中国药理学与毒理学杂志》
CAS
北大核心
2023年第9期655-663,共9页
Chinese Journal of Pharmacology and Toxicology
