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高压氧疗法可恢复衰老和肥胖大鼠的认知功能和海马病理学。

Hyperbaric oxygen therapy restores cognitive function and hippocampal pathologies in both aging and aging-obese rats.

机构信息

Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; Center of Excellence in Cardiac Electrophysiology, Chiang Mai University, Chiang Mai, 50200, Thailand.

Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; Center of Excellence in Cardiac Electrophysiology, Chiang Mai University, Chiang Mai, 50200, Thailand.

出版信息

Mech Ageing Dev. 2021 Apr;195:111465. doi: 10.1016/j.mad.2021.111465. Epub 2021 Mar 1.

Abstract

The population of obese-elderly has increased prominently around the world. Both aging and obesity are major factors of neurodegeneration. The present study hypothesizes that HBOT attenuates metabolic disturbance, cognitive decline, hippocampal pathologies in aging and aging-obese model. Sixty Wistar rats were separated into 2 groups to receive normal-diet (ND) or high-fat diet (HFD) for 22 weeks. At week 13, ND rats were divided into two subgroups to receive vehicle (0.9 % NSS, s.c) or d-gal (150 mg/kg/d, s.c) for total 10 weeks. HFD rats were injected only d-gal (150 mg/kg/d, s.c; HFDD) for total 10 weeks. At week 20, rats in each subgroup were given sham-treatment (1ATA, 80 L/min, 80 min/day), or HBOT (2ATA, pure O, 250 L/min, 80 min/day) for 14 days. Novel object location test, metabolic parameters, and hippocampal pathologies were determined after HBOT. d-gal induced insulin resistance, increased oxidative stress, autophagy impairment, microglial hyperactivation, apoptosis, synaptic dysplasticity which resulted in cognitive impairment. d-gal-treated HFD-fed rats had the highest levels of oxidative stress, apoptosis, dendritic spine loss. HBOT attenuated insulin resistance, cognitive impairment, hippocampal aging and pathologies in both models. These findings suggest that HBOT restored insulin sensitivity, hippocampal functions, cognition in aging and aging-obese models.

摘要

肥胖老年人的人口在全球范围内显著增加。衰老和肥胖都是神经退行性变的主要因素。本研究假设高压氧治疗(HBOT)可减轻衰老和衰老-肥胖模型中的代谢紊乱、认知衰退和海马病理学。60 只 Wistar 大鼠分为 2 组,分别接受正常饮食(ND)或高脂肪饮食(HFD)22 周。第 13 周时,ND 大鼠分为两组,分别接受 vehicle(0.9%生理盐水,sc)或 d-gal(150mg/kg/d,sc)共 10 周。HFD 大鼠仅接受 d-gal(150mg/kg/d,sc;HFDD)共 10 周。第 20 周时,每个亚组的大鼠分别接受假处理(1ATA,80L/min,80min/d)或 HBOT(2ATA,纯 O,250L/min,80min/d)14 天。HBOT 后测定新物体定位测试、代谢参数和海马病理学。d-gal 诱导胰岛素抵抗、增加氧化应激、自噬受损、小胶质细胞过度激活、细胞凋亡、突触发育不良,导致认知障碍。d-gal 处理的 HFD 喂养大鼠的氧化应激、细胞凋亡、树突棘丢失水平最高。HBOT 减轻了两种模型中的胰岛素抵抗、认知障碍、海马衰老和病理学。这些发现表明 HBOT 恢复了衰老和衰老-肥胖模型中的胰岛素敏感性、海马功能和认知。

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