武汉云克隆科技股份有限公司

Abstract: Upper airway obstruction (UAO) can lead to abnormal growth hormone (GH) homeostasis and growth retardation but the mechanisms are unclear. We explored the effect of UAO on hypothalamic GH-releasing hormone (GHRH), which has a role in both sleep and GH regulation. The tracheae of 22-day-old rats were narrowed; UAO and sham-operated animals were sacrificed 16 days post-surgery. To stimulate slow-wave sleep (SWS) and GH secretion, rats were treated with ritanserin (5-HT(2) receptor antagonist). Sleep was measured with a telemetric system. Hypothalamic GHRH, hypothalamic GHRH receptor (GHRHR) and GH receptor, and orexin were analysed using ELISA, real-time PCR and Western blot. UAO decreased hypothalamic GHRH, GHRHR and GH receptor levels, while orexin mRNA increased (p<0.01). In UAO rats, the duration of wakefulness was elevated and the duration of SWS, paradoxical sleep and slow-wave activity was reduced (p<0.001). Ritanserin alleviated these effects, i.e. normalised hypothalamic GHRH content, decreased wake duration, increased duration and depth of SWS, and attenuated growth impairment (p<0.001). Here, we present evidence that growth retardation in UAO is associated with a reduction in hypothalamic GHRH content. Our findings show that abnormalities in the GHRH/GH axis underlie both growth retardation and SWS-disorder UAO.

摘要：上呼吸道阻塞（UAO）可导致异常生长激素（GH）体内平衡和生长迟缓，但机制尚不清楚。我们探讨了UAO对下丘脑GH释放激素（GHRH）的影响，GHRH在睡眠和GH调节中都起作用。 22日龄大鼠的气管狭窄; UAO和假手术的动物在手术后16天处死。为了刺激慢波睡眠（SWS）和GH分泌，用ritanserin（5-HT（2）受体拮抗剂）处理大鼠。用遥测系统测量睡眠。使用ELISA，实时PCR和蛋白质印迹分析下丘脑GHRH，下丘脑GHRH受体（GHRHR）和GH受体以及食欲肽。 UAO降低下丘脑GHRH，GHRHR和GH受体水平，而orexin mRNA增加（p <0.01）。在UAO大鼠中，觉醒的持续时间升高，SWS持续时间，自相矛盾的睡眠和慢波活动减少（p <0.001）。 Ritanserin缓解了这些影响，即归一化的下丘脑GHRH含量，唤醒持续时间减少，SWS持续时间和深度增加以及衰减的生长受损（p <0.001）。在这里，我们提出的证据表明，UAO的发育迟缓与下丘脑GHRH含量的减少有关。我们的研究结果表明GHRH / GH轴异常是发育迟缓和SWS紊乱UAO的基础。

使用试剂原文信息：Hypothalamic GHRH was determined by ELISA kit (USCN Life Science Inc., Wuhan, China) according to the manufacturer’s instructions on day 16.