Study on sudden cardiovascular death in animal model of sleep apnea syndrome

我们已经开发了可以使许多大鼠长时间暴露于间歇性缺氧（IH）的装置。IH 3周可诱导幼鼠心肌细胞自噬，通过降解受损器官和变性蛋白质来预防心力衰竭，但在成年（9月龄）大鼠（2月龄），IH 3周可通过激活肺动脉（PA）酶和相互抑制一氧化氮（NO）合酶（NOS）而诱导肺动脉（PA）高血压（PAH）。在幼年大鼠中，IH 6周诱导巨噬细胞的募集，增强PA周围β 3-肾上腺素能受体诱导型NOS的表达。在交感神经麻痹的情况下，巨噬细胞衍生的NO预防PAH。在高脂饲料喂养的幼鼠中，4- 5d的IH通过激活内皮素或凝血系统诱导PAH。总体而言，IH诱导适应性机制，以防止心力衰竭或PAH在年轻和健康的艺术，但IH发挥有害作用，在成年和高血压大鼠。

We have exploited apparatus that can expose many rats to intermittent hypoxia (IH) for a long period. IH for 3 weeks induces autophagy in the myocardium of the young rats, thereby preventing heart failure through degradation of injured organnels and degenerated proteins.In adult (9 month) but not young (2 month) rats, IH for 3 weeks induces pulmonary artery (PA) hypertension (PAH) through activation of arginase and reciprocal inhibition of nitric oxide (NO) synthase (NOS). In young rats, IH for 6 weeks induces recruitement of macrophage with enhanced expression of beta3-adrenergic receptor-inducible NOS around PAs. With sympathetic overdrive, the macrophage-derived NO prevents PAH. In young rats fed high fat diet, IH for 4-5days induced PAH through activation of endothelin or coagulation systems. Collectively, IH induces adaptative mechanisms to prevent heart failure or PAH in young and healthy arts, but IH exerts deleterious effects in adult and hyperlipidemic rats.