Orexin-A and respiration in a rat model of smoke-induced chronic obstructive pulmonary disease
Orexin-A and respiration in a rat model of smoke-induced chronic obstructive pulmonary disease
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DOI：
10.1111/j.1440-1681.2010.05411.x
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发表时间：
2010-10-01
影响因子：
2.9
通讯作者：
Shen, Lin-Lin
中科院分区：
文献类型：
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作者：
Liu, Zi-Bing;Song, Na-Na;Shen, Lin-Lin
P>1。食欲素是在下丘脑中合成的神经肽，其调节许多生理功能，包括能量稳态、应激反应、睡眠/觉醒状态等。现在出现食欲素也可以调节呼吸，但很少有人知道它们是如何做到这一点的，特别是在慢性阻塞性肺疾病（COPD）中。本研究采用香烟烟雾诱导的慢性阻塞性肺疾病（COPD）大鼠模型，探讨食欲素A（orexin-A）在下丘脑和延髓的表达及其对呼吸的影响.将Sprague-Dawley大鼠暴露于香烟烟雾中（每天两次，每次1小时），持续12周。检测肺功能及炎症、肺气肿相关的病理改变，证实COPD模型的有效性.放射免疫法测定，烟雾暴露组大鼠下丘脑和延髓食欲素A水平高于对照组。此外，通过实时定量聚合酶链反应测定，烟雾暴露大鼠下丘脑中前食欲素原（PPO）mRNA和延髓中食欲素OX 1受体mRNA的表达高于对照大鼠。4.烟雾暴露组大鼠下丘脑orexin-A阳性神经元和延髓腹外侧区OX 1、OX 2受体阳性神经元数量均高于对照组.与对照组相比，烟雾暴露组大鼠在前Botzinger复合体中微量注射orexin-A（1 μ mol/L，0.1 μ L）可更大程度地增强膈神经放电（分别为61%和36%）.本研究的结果表明，在烟雾暴露的大鼠呼吸活动的增加是由于食欲素A的增加，以及在延髓腹外侧食欲素受体的上调。
P>1. Orexins are neuropeptides synthesized in the hypothalamus that regulate many physiological functions, including energy homeostasis, stress responses, sleep/wake states etc. It is now emerging that orexins may also regulate breathing, but little is known as to how they do this, particularly in chronic obstructive pulmonary disease (COPD). In the present study, we used a rat model of cigarette smoke-induced COPD to investigate orexin-A expression in the hypothalamus and medulla and its effect on respiration.2. Sprague-Dawley rats were exposed to cigarette smoke (1 h twice daily) for 12 weeks. Lung function and pathological changes associated with inflammation and emphysema were determined to confirm the validity of the COPD model.3. Hypothalamic and medullary orexin-A levels, as determined by radioimmunoassay, were higher in smoke-exposed than control rats. Furthermore, the expression of prepro-orexin (PPO) mRNA in the hypothalamus and orexin OX1 receptor mRNA in the medulla, as determined by real-time quantitative polymerase chain reaction, was higher in smoke-exposed than control rats.4. The number of orexin-A-positive neurons in the hypothalamus and OX1 and OX2 receptor-positive neurons in the ventrolateral medulla was higher in smoke-exposed than control rats.5. Microinjection of orexin-A (1 mu mol/L, 0.1 mu L) into the pre-Botzinger complex enhanced phrenic nerve discharge to a greater extent in smoke-exposed compared with control rats (61% vs 36%, respectively).6. The findings of the present study demonstrate that the increased respiratory activity in smoke-exposed rats is due to an increase in orexin-A as well as upregulation of orexin receptors in the ventrolateral medulla.