The Effect Of Chronic Intermittent Hypoxia On Hypothalamic-pituitary-adrenal Axis In Rats

Objective: To set up a chronic intermittent hypoxic animal model, as an experimental platform for further study of the pathogenesis of OSAHS. By studying the function and structural changes of chronic intermittent hypoxia(CIH) and removal of hypoxia(RH) on hypothalamic- pituitary-adrenal axis in Sprague-Dawley rats, including changes of CRH,ACTH , COR in blood serum and their interrelation, observing the ultrastructural changes in rats hypothalamus, pituitary and adrenal by electron microscopy. Explore the possible mechanisms of hypothalamic pituitary-adrenal axis'dysfunction in patients with CIH, and to provide a theoretical basis for the treatment of patients with OSAHS.Methods: Experiments were performed on 24 three-month-old male Sprague-Dawley rats, they were randomly assigned to three experimental groups (n=8/group): unhandled control group (UC), chronic intermittent hypoxia group (CIH), and Removal of hypoxia group (RH). Rats in UC group were raised normally, those in CIH group suffered 8h intermittent hypoxia everyday, the duration of experiment was 4 weeks, and those in RH group was the same as those in CIH group in previous 4 weeks and were raised normally in later 4 weeks. All the rats were killed after experiment. CRH,ACTH,COR in serum of rats were measured by radioimmunoassay, and ultramicrostructure of rats'hypothalamus, pituitary and adrenal were observed by electron microscope.Results: The level of the rats'CRH,ACTH,COR in serum in the CIH group increased significantly than those in the UC group and RH group (P<0.01), but it is not true between UC group and RH group (P>0.05);Ultrastructure of hypothalamus, pituitary, adrenal in the CIH group showed strong metabolic changes. The Golgi complex and mitochondria in hypothalamus was increased significantly, mitochondrial was swelling, transparency uesicae and secretory granules were increased in cytoplasmic; pituitary basophilic cells'secretory granules was increased,mitochondrial swelling and smooth endoplasmic reticulum; lesions of the adrenal cortex fascicular was obviously,showed reduced intracellular lipid droplets, cell swelling, mitochondrial cavitations, smooth endoplasmic reticulum and Golgi apparatus extension and nuclear membrane gap widened.Conclusions: Chronic intermittent hypoxia can activate the hypothalamic-pituitary-adrenal axis of rats , feedback regulation is disordered. Reoxygenation can make it back to normal.