Differences in sleep-induced hypoxia between A/J and DBA/2J mouse strains

Differences in sleep-induced hypoxia between A/J and DBA/2J mouse strains
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DOI:
10.1164/rccm.200304-462oc
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发表时间:
2003-12-15
影响因子:
24.7
通讯作者:
O'Donnell, CP
O'Donnell, CP
中科院分区:
医学1区
文献类型:
--
作者:
Rubin, AE;Polotsky, VY;O'Donnell, CP

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在阻塞性睡眠呼吸暂停中,低氧刺激敏感性可能会影响上呼吸道阻塞引起的低氧应激和睡眠中断的程度。我们在两个具有低(A/J)和高(DBA/2 J)低氧刺激敏感性的近交系小鼠中诱导(1)睡眠诱导的低氧(SIH)或(2)无低氧的睡眠片段化(SF)5天(12小时光/暗循环)。在SIH期间,A/J小鼠的觉醒时间(26.4 +/- 1.1对21.3 +/- 1.5秒,p < 0.025)和缺氧暴露的严重程度(最低Fi(O2):11.5 +/- 0.4对13.6 +/-0.1%,p < 0.002)大于DBA/2 J小鼠。此外,在SIH期间,A/J小鼠比DBA/2 J小鼠具有更高的缺氧事件频率(每24小时640 +/- 29对368 33次事件,p < 0.001)和总睡眠时间(每24小时47.5 +/-2.8%对26.5 +/- 2.4%,p < 0.0001)。相比之下,两种菌株在SF期间的事件特征和总睡眠时间是相同的。此外,在亮相,与暗相相比,两种品系在SIH和SF期间显示更长(p < 0.01)的唤醒时间。我们的结论是遗传背景可以影响呼吸事件和睡眠结构在SIH和觉醒阈值是受昼夜变化。我们的数据表明,低氧敏感性低的个体发生阻塞性睡眠呼吸暂停缺氧相关并发症的风险可能更大。
In obstructive sleep apnea, hypoxic ventilatory sensitivity may affect the degree of hypoxic stress and sleep disruption that occurs in response to upper airway obstruction. We induced (1) sleep-induced hypoxia (SIH) or (2) sleep fragmentation (SF) without hypoxia for 5 days (12-hour light/dark cycle) in two inbred mouse strains with low (A/J) and high (DBA/2J) hypoxic ventilatory sensitivities. During SIH, the time to arousal (26.4 +/- 1.1 vs. 21.3 +/- 1.5 seconds, p < 0.025) and the severity of hypoxic exposure (nadir Fi(O2): 11.5 +/- 0.4 vs. 13.6 +/- 0.1%, p < 0.002) was greater in A/J than DBA/2J mice. Furthermore, A/J mice had a greater frequency of hypoxic events (640 +/- 29 vs. 368 33 events per 24 hours, p < 0.001) and total sleep time (47.5 +/- 2.8% vs. 26.5 +/- 2.4% per 24 hours, p < 0.0001) during SIH than DBA/2J mice. In contrast, the event characteristics and total sleep time during SF were the same in both strains. Furthermore, in the light phase, both strains showed a longer (p < 0.01) time to arousal during SIH and SF compared with the dark phase. We conclude that genetic background can influence respiratory events and sleep architecture during SIH and that the arousal threshold is subject to circadian variation. Our data imply that individuals with low hypoxic sensitivity may be at a greater risk for hypoxia-related complications of obstructive sleep apnea.