武汉云克隆科技股份有限公司

Abstract

RATIONALE:

Exposure to intermittent hypoxia (IH), such as occurs in sleep-disordered breathing, is associated with substantial cognitive impairments, oxidative stress and inflammation, and increased neuronal cell losses in brain regions underlying learning and memory in rats. Physical activity (PA) is now recognized as neuroprotective in models of neuronal injury and degeneration.

OBJECTIVES:

To examine whether PA will ameliorate IH-induced deficits.

METHODS:

Young adult Sprague-Dawley rats were randomly assigned to one of four treatment groups including normal activity (NA) or PA for 3 months and then subjected to either normoxia (RA) or exposure to IH during the light phase during the last 14 days.

MEASUREMENTS AND MAIN RESULTS:

Significant impairments in IH-exposed rats emerged on both latency and pathlength to locate the hidden platform in a water maze and decreased spatial bias during the probe trials. These impairments were not observed in PA-IH rats. In addition, the PA-IH group, relative to NA-IH, conferred greater resistance to both lipid peroxidation and 8-hydroxy-2'-deoxyguanosine (DNA damage) in both the cortex and hippocampus. In support of a neuroprotective effect from PA, PA-IH versus NA-IH rats showed greater AKT activation and neuronal insulin growth factor-1 in these regions.

CONCLUSIONS:

Behavioral modifications such as increased physical activity are associated with decreased susceptibility to IH-induced spatial task deficits and lead to reduced oxidative stress, possibly through improved preservation of insulin growth factor-1-Akt neuronal signaling. Considering the many advantages of PA, interventional strategies targeting behavioral modifications leading to increased PA should be pursued in patients with sleep-disordered breathing.

摘要：

原理:

出现间歇性缺氧（IH），如在睡眠障碍性呼吸中出现，与严重的认知障碍、氧化应激和炎症有关，以及在大鼠中，增加了学习和记忆的大脑区域神经元细胞的损失。体育活动（PA）现在被认为在神经元损伤和退化模型中有神经保护功能。

目的:

检测是否体育活动会改善间歇性缺氧诱导的缺陷。

方法:

年轻的成年SD大鼠被随机分到四个处理组中的一个，包括正常活动（NA）或体育活动三个月，然后在最后的14天里，放入常氧环境或轻微间歇性缺氧环境。

检测及主要结果:

通过评价在水迷宫中找到隐藏平台的延迟时间、探测距离和在探测实验中减少空间偏差，发现间歇性缺氧组大鼠出现显著性损伤。这些损伤没有在体育活动-间歇性缺氧组大鼠身上观察到。此外，相对于正常活动-间歇性缺氧组，体育活动-间歇性缺氧组在皮质和海马区都对脂质过氧化氢和8-羟基-2-脱氧鸟苷（DNA损伤）有更大的抵抗力。为了支撑体育活动的神经保护作用，在这些区域，体育活动-间歇性缺氧组比正常活动-间歇性缺氧组大鼠显示出更大的AKT激活作用和神经元胰岛素生长因子1水平。

结论:

行为上的改变，如增加体育活动，与降低间歇性缺氧诱发的空间感缺陷的易感性有关，并导致氧化应激的减少，这种现象可能是通过改善胰岛素生长因子-1-akt神经信号传导导致的。考虑到体育活动的众多优点，在有睡眠呼吸障碍的患者中，应采取干预策略，增强体育锻炼。

使用试剂原文信息：In addition, hippocampal tissue lysates were prepared and IGF-1-like immunoreactivity was assessed using a high-sensitivity ELISA assay (Uscn Life Science Inc. Wuhan, PR China; cat # E0050Ra), which has a linear range of 15.6 to 1,000 pg/ml and a sensitivity of 7.9 pg/ml.