Projektakademie Medizintechnik - simulation of obstructive sleepapnea syndrome (OSAS) in a mouse model using "LivingLab"

项目学院医疗技术 - 使用“LivingLab”在小鼠模型中模拟阻塞性睡眠呼吸暂停综合征 (OSAS)

• 批准号: 357750099
• 负责人: Professor Dr. Keywan Sohrabi
• 金额: --
• 依托单位: Fachbereich 05 - Gesundheit
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/357750099?language=en
• 关键词: Projektakademie; Medizintechnik; simulation; obstructive; sleepapnea

Background: The incidence of obstructive sleep apnea syndrome (OSAS) is rising in western industrial nations. The sleep disorder autonomously represents a risk factor for high blood pressure, arteriosclerosis and lately also type 2 diabetes. Hypoxia, which is caused by apnea phases during sleep (15 to >100/h) plays a major role in this process. This phenomenon has been simulated in a mouse model through chronic intermittent hypoxia (CIH). However, the CIH mouse model has not been able to show and solve pathophysiology entirely.Especially the occurrence of insulin resistance as a main factor for type 2 diabetes could not be reliably verified, even after several weeks of OSAS simulation. A determining factor could be differences in microcirculation in the models skeletal muscles. Preliminary studies showed for the first time that capillarization of the skeletal muscle significantly decreases in the majority of OSAS patients, whereas it significantly increases in the CIH mouse model. This aspect could be the crucial weak point of the previous CIH mouse model.Aim of the project: To realistically and entirely reproduce the massive metabolic and vascular risks of the skeletal muscle in OSAS to eventually and for the first time evaluate pathophysiology and (if possible) therapeutic approaches in a realistic way.

背景：阻塞性睡眠呼吸暂停综合征（OSAS）的发病率在西方工业国家呈上升趋势。睡眠障碍是高血压、动脉硬化以及最近出现的2型糖尿病的一个危险因素。睡眠期间呼吸暂停阶段（15 ~ 100/h）引起的缺氧在这一过程中起主要作用。通过慢性间歇缺氧（CIH）在小鼠模型中模拟了这一现象。然而，CIH小鼠模型还不能完全显示和解决病理生理问题。特别是胰岛素抵抗的发生作为2型糖尿病的主要因素，即使经过几周的OSAS模拟也无法得到可靠的验证。一个决定因素可能是模型骨骼肌微循环的差异。初步研究首次表明，大多数OSAS患者骨骼肌的毛细血管化明显减少，而CIH小鼠模型的毛细血管化明显增加。这方面可能是先前的CIH小鼠模型的关键弱点。该项目的目的是：真实和完整地再现OSAS骨骼肌的大量代谢和血管风险，最终并首次以现实的方式评估病理生理学和（如果可能的话）治疗方法。