Everson Carol A, Thalacker Christa D, Hogg Neil
Department of Neurology, The Medical College of Wisconsin, Neurology Research 151, VAMC, 5000 West National Ave., Milwaukee, WI 53295, USA.
Am J Physiol Regul Integr Comp Physiol. 2008 Dec;295(6):R2067-74. doi: 10.1152/ajpregu.90623.2008. Epub 2008 Oct 22.
Sleep is understood to possess recuperative properties and, conversely, sleep loss is associated with disease and shortened life span. Despite these critical attributes, the mechanisms and functions by which sleep and sleep loss impact health still are speculative. One of the most consistent, if largely overlooked, signs of sleep loss in both humans and laboratory rats is a progressive increase in circulating phagocytic cells, mainly neutrophils. The destination, if any, of the increased circulating populations has been unknown and, therefore, its medical significance has been uncertain. The purpose of the present experiment was to determine the content and location of neutrophils in liver and lung tissue of sleep-deprived rats. These are two principal sites affected by neutrophil migration during systemic inflammatory illness. The content of neutrophils in the intestine also was determined. Sleep deprivation in rats was produced for 5 and 10 days by the Bergmann-Rechtschaffen disk method, which has been validated for its high selectivity under freely moving conditions and which was tolerated and accompanied by a deep negative energy balance. Comparison groups included basal conditions and 48 h of sleep recovery after 10 days of sleep loss. Myeloperoxidase (MPO), an enzyme constituent of neutrophils, was extracted from liver, lung, and intestinal tissues, and its activity was determined by spectrophotometry. Leukocytes were located in vasculature and interstitial spaces in the liver and the lung by immunohistochemistry. Heme oxygenase-1, also known as heat shock protein-32 and a marker of cellular stress, and corticosterone also were measured. The results indicate neutrophil migration into extravascular liver and lung tissue concurrent with cell stress and consistent with tissue injury or infection induced by sleep loss. Plasma corticosterone was unchanged. Recovery sleep was marked by increased lung heme oxygenase-1, increased intestinal MPO activity, and abnormally low corticosterone, suggesting ongoing reactive processes as a result of prior sleep deprivation.
睡眠被认为具有恢复性，相反，睡眠不足与疾病和寿命缩短有关。尽管有这些关键特性，但睡眠和睡眠不足影响健康的机制和功能仍具有推测性。在人类和实验大鼠中，睡眠不足最一致（但很大程度上被忽视）的迹象之一是循环吞噬细胞（主要是中性粒细胞）逐渐增加。循环细胞数量增加后的去向（如果有）一直未知，因此其医学意义也不确定。本实验的目的是确定睡眠剥夺大鼠肝脏和肺组织中中性粒细胞的含量和位置。这是全身炎症性疾病期间受中性粒细胞迁移影响的两个主要部位。还测定了肠道中中性粒细胞的含量。采用伯格曼 - 雷希特沙芬圆盘法使大鼠睡眠剥夺5天和10天，该方法在自由活动条件下具有高选择性且已得到验证，大鼠能耐受且伴有深度负能量平衡。对照组包括基础状态以及睡眠剥夺10天后48小时的睡眠恢复情况。从肝脏、肺和肠道组织中提取中性粒细胞的酶成分髓过氧化物酶（MPO），并用分光光度法测定其活性。通过免疫组织化学确定白细胞在肝脏和肺的血管和间质空间中的位置。还测量了血红素加氧酶 -1（也称为热休克蛋白 -32，是细胞应激的标志物）和皮质酮。结果表明中性粒细胞迁移到血管外的肝脏和肺组织，同时伴有细胞应激，这与睡眠不足引起的组织损伤或感染一致。血浆皮质酮未发生变化。恢复睡眠的特征是肺血红素加氧酶 -1增加、肠道MPO活性增加以及皮质酮异常低，这表明先前睡眠剥夺导致持续的反应过程。
