Salivary CRH as a biomarker to evaluate individual responses to hypoxia
【摘要】：正Hypoxia is not only a component of many disease processes,but occurs under physiological conditions. When oxygen uptake becomes limited or oxygen consumption becomes excessive,cellular metabolism decreases oxidative phosphorylation and relies on glycolysis as the primary ATP production pathway by upregulating the expression of glycolytic enzymes,such as lactate dehydrogenase(LDH) and its isoforms.The hypothalamic-pituitary -adrenal(HPA) axis,one of the principal pathways which respond to stress,can be active under hypoxia. The HPA axis plays roles via the hypothalamic hormone,corticotrophin releasing hormone(CRH),which regulates the secretion of adrenocorticotrophin from the anterior pituitary,and then regulates the secretion of glucocorticoids, such as Cortisol in humans and corticosterone in rats.We designed two type of exercise,climbing up stairs to the 18~(th) floor within 4 min(about 80 m in height and 130 m in distance) and bicycling for 10 min at a constant power. We developed a new method for evaluating the hypoxic response using 5μL of saliva to test CRH and Cortisol. Forty-eight volunteers from Zhejiang University(20-24 years old,males and females) supplied saliva and blood samples for assay.Samples were collected at 7:00,10:00,11:00(before and after exercise) and 23:00.Heart rate and saturated O_2(So_2,finger monitor) were measured as indicators of oxygen consumption.Both exercises led to an increase of salivary and plasma CRH,Cortisol and LDH.The levels of salivary CRH,Cortisol and LDH were associated with the intensity of hypoxia.We found the increased CRH,Cortisol,and LDH in saliva and plasma, decreased So_2 after exercise,and the change of salivary CRH and Cortisol had good positive correlations with the changes of the plasma CRH and Cortisol(correlation coefficient,0.84 and 0.87) after exercise.Results showed that salivary CRH and Cortisol changed in parallel with plasma CRH and Cortisol.The method using salivary CRH and Cortisol is simple and noninvasive,and the data suggest that the level of salivary CRH and Cortisol can be used to evaluate individual responses to hypoxia.