Laboratorio de Neurobiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Adv Exp Med Biol. 2018;1071:69-74. doi: 10.1007/978-3-319-91137-3_8.
Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH), which is considered the main factor for developing hypertension. Sympathetic overflow, oxidative stress and inflammation have been associated with the CIH-induced hypertension. In rats exposed to CIH mimicking OSA, intermittent hypoxia enhanced carotid body (CB) chemosensory discharge, leading to an increase in arterial blood pressure in 3-5 days. In addition, CIH increases the CB levels of proinflammatory cytokines IL-1β, IL-6 and TNF-α in the CB. Proinflammatory molecules have been also involved in neurogenic hypertension acting on brain cardiovascular centers, like the nucleus of the solitary tract (NTS), which is the primary site for afferent CB inputs. Accordingly, we aim to study if proinflammatory cytokines in the NTS may play a role in the hypertension induced by CIH. Male Sprague-Dawley rats 250 g were exposed to CIH (5% O, 12 times/h, 8 h/day) for 7-28 days. Brains were removed and processed to measure IL-1β, IL-6 and TNF-α in the NTS using qPCR and immunofluorescence. The mRNA levels were significantly augmented in the NTS of rats exposed during 21 days to CIH compared with control animals. In addition, a significant increase of IL-1β, IL-6 and TNF-α immunofluorescence was found in the NTS at day 28 of CIH exposure compared with control rats. Present results suggest that proinflammatory cytokines in the NTS may contribute to the maintenance of hypertension in CIH-exposed animals.
阻塞性睡眠呼吸暂停（OSA）的特征是慢性间歇性低氧（CIH），这被认为是高血压发展的主要因素。交感神经溢出、氧化应激和炎症与 CIH 引起的高血压有关。在模拟 OSA 的 CIH 暴露的大鼠中，间歇性低氧增强了颈动脉体（CB）的化学感觉放电，导致动脉血压在 3-5 天内升高。此外，CIH 增加了 CB 中促炎细胞因子 IL-1β、IL-6 和 TNF-α的水平。促炎分子也参与了作用于脑心血管中枢的神经原性高血压，如孤束核（NTS），这是 CB 传入输入的主要部位。因此，我们旨在研究 NTS 中的促炎细胞因子是否在 CIH 引起的高血压中起作用。250 克雄性 Sprague-Dawley 大鼠暴露于 CIH（5%O，12 次/小时，每天 8 小时）7-28 天。取出大脑并进行处理，使用 qPCR 和免疫荧光法测量 NTS 中的 IL-1β、IL-6 和 TNF-α。与对照动物相比，暴露于 CIH 21 天的大鼠 NTS 中的 mRNA 水平显著增加。此外，在 CIH 暴露 28 天时，NTS 中还发现了 IL-1β、IL-6 和 TNF-α 免疫荧光的显著增加。目前的结果表明，NTS 中的促炎细胞因子可能有助于维持 CIH 暴露动物的高血压。
