武汉云克隆科技股份有限公司

Abstract: Upper airway obstruction (UAO) can lead to abnormal growth hormone homeostasis and growth retardation by unclear mechanisms. We explored the effect of UAO on hypothalamic growth hormone releasing hormone (GHRH), which has a role in both sleep and growth hormone 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 and growth hormone secretion, rats were treated with ritanserin (5-HT2 receptor antagonist). Sleep was measured with telemetric system. Hypothalamic GHRH, hypothalamic GHRH and growth hormone receptors, and orexin were analyzed using ELISA, real-time PCR, and Western immunoblot.

UAO decreased hypothalamic GHRH, GHRH and growth hormone receptors levels, while orexin mRNA increased (p<0.01). In UAO rats the duration of wakefulness was elevated and the duration of slow wave sleep (SWS), paradoxical sleep, and slow wave activity were reduced (p<0.001). Ritanserin alleviated these effects, i.e., normalized 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 the abnormalities in GHRH/growth hormone axis underlie both growth retardation and SWS disorder UAO. 

摘要：上呼吸道阻塞（UAO）可导致异常的生长激素内环境平衡由于机制不明而导致发育迟缓。我们探讨了UAO的影响下丘脑生长激素释放激素（GHRH），它们在两者中都有作用睡眠和生长激素调节。

22日龄大鼠的气管狭窄; UAO和假手术的动物是在手术后16天牺牲。刺激慢波睡眠和生长激素分泌，用ritanserin（5-HT2受体拮抗剂）处理大鼠。睡了用遥测系统测量。下丘脑GHRH，下丘脑GHRH和生长激素受体和食欲肽的分析使用ELISA，实时PCR，和Western免疫印迹。

UAO降低下丘脑GHRH，GHRH和生长激素受体水平，而orexin mRNA增加（p <0.01）。在UAO大鼠中，觉醒的持续时间是升高和慢波睡眠（SWS），矛盾睡眠和慢波的持续时间活性降低（p <0.001）。 Ritanserin缓解了这些影响，即正常化下丘脑GHRH含量，唤醒持续时间缩短，持续时间和深度增加SWS和衰减的生长受损（p <0.001）。

在这里我们提出的证据表明，UAO的发育迟缓与减少有关在下丘脑GHRH含量。我们的研究结果表明，GHRH /生长激素轴是发育迟缓和SWS疾病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.