Study Of Plasma Orexin-A Levels In Patients With Obstructive Sleep Apnea-hypopnea Syndrome

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a common sleep disorder characterized by recurrent episodes of upper airway collapse and obstruction, recurrent oxyhemoglobin desaturation and frequent arousals during sleep. The pathophysiology of the OSAHS is complex. Obesity and visceral fat accumulation are risk factors for the development of OSAHS.The orexins, also know as hypocretins, are neropeptides produced by lateral hypothalamus area (LHA). Orexin-A and orexin-B are the two peptides found in mammals. These neuropeptides act via binding and activating two closely related orexin receptors—G-protein coupled receptors, named OXIR and 0X2R. Orexin-A with two disulfide bonds and high affinity to fat can rapidly cross blood-brain barrier by simple diffusion, whereas orexin-B is a linear peptide with low affinity to fat and cannot cross the blood-brain barrier. Currently, most international researches are focused on orexin A. The initial research suggested that orexin-A affects food intake. Many animal research results showed that orexin can increase appetite and weight gain. Immunohitochemical studies discovered that orexin neurons can project their fibers extensively to the entire central nervous system, which indicates the multifunction of orexin. Recent researches report that orexin is involved in adjusting sleep-wake cycle. However, it is unclear that the correlation between obesity and plasma orexin A levels in patients with OSAHS. Here we present the research of the correlation and clinical significance of plasma orexin-A levels in patients with OSAHS.Objective and MethodsSixty patients diagnosed with OSAHS by clinical trial and polysomnography(PSG) were selected as testing group. The comparison group consists of 40 adults without snoring, being studied by PSG and with the apnea-hypopnea index (AHI )< 5. Based on "The Asia-Pacific Perspective: Redefining obesity and its Treatment" by WHO, the testing group is divided into obese OSAHS and non-obese OSAHS groups with 30 patients each. Using the same standard, the comparison group is also divided into obese and non- obese groups with 20 adults each.PSG is used to record eletroencephalogram (EEG), electrooculogram (EOG), eletromyogram (EMG), electrocardiogram, thermistors for nasal and oral airflow, body position, thoracic and abdominal movement and oxygen saturation. AHI, arousal index, SLT.90% and ODI4 are measured. Blood samples (3ml per subject) were collected from the vein with empty stomach between 6:00 AM and 7:00 AM after undergoing the PSG. Plasma orexin-A levels were measured by radioimmunoassay. SPSS 10.0 software package is used to perform statistically analysis.Results1. Age and sex ratio are statistical insignificance ( P > 0.05). The body mass index (BMI) in the obese OSAHS group and the obese comparison group are statistical insignificance as well as non-obese OSAHS group and non-obese comparison group (P>0.05).2. The plasma orexin-A levels is significant higher in the OSAHS group than the non- OSAHS group(P<0.01). The statistical analysis cannot distinguish plasma orexin-A levels between the obese group and the non-obese group comparison group (P>0.05) . There is no interaction effect between Obesity and OSAHS(P>0.05).3. There is no correlation between the plasma orexin-A levels and BMI.4. Based on AHI, divide the OSAHS groups into high, medium and low subgroups. Plasma orexin-A levels in the high AHI groups are higher than medium and low AHI groups.5. There is positive correlation between the plasma orexin-A levels and arousal index, SLT90%, AHI, ODI4 in OSAHS groups.DiscussionOrexin A, a neropeptide produced by lateral hypothalamus area, affects food intake. Recent researches indicate that orexin may have many nerve regulatory functions. It not only affects food intake, but also is involved in regulatory networks that controls sleep-wake cycle, glucose metabolism, autonomic nervous system and reproduction system. The frequent arousals during sleep of patients with OSAHS indicate that there may be related between orexin-A and OSAHS. This study shows plasma orexin-A levels in the obese OSAHS group is a little bit higher than non-obese OSAHS group, and it is also higher obese comparison group than non-obese comparison group. However, the difference shows no statistically significance. Furthermore, there is no correlation between plasma orexin-A levels and BMI. Therefore, we believe orexin-A can affect food intake when lower glucose level and thus, it is implicated in regulating energy balance after food intake. The producing level of orexin-A should be correlated with obesity based on its producing area and the physiological role when affecting food intake. It is also reasonable to believe that the orexin-A level in the cerebrospinal fluid (CSF) can prove it is regulating energy balance. Although orexin-B has less effect in controlling food intake in central nerve system than orexin-A, the property of not cross blood-brain barrier can prolong the medical effectiveness and thus, regulate the obese development. This study also found plasma orexin-A levels in OSAHS groups is significant higher that comparison groups, and plasma orexin-A levels is higher when AHI is higher. There is a positive correlation between the plasma orexin-A levels and AHI, arousal index, SLT90%, ODI4 in patients with OSHAS. This indicates that plasma orexin-A levels is higher when OSAHS is more serious. A possible reason of higher orexin-A level may be: frequent breathing suspending and low airflow will cause low blood oxygen and cause more activity of lateral hypothalamus area, thus producing more orexin-A and exciting the monoaminergic (REM-off) cells, eventually suppress cholinergic (REM-on) cells and more wakeups.Conclusions1. Orexin-A may regulate energy balance in short term. However, it isn't the direct factor contributing to the obesity.2. Increased plasma orexin-A levels lead to more arousal in patients with OSAHS, which indicates that orexin-A levels may play a key role in regulating sleep-wake cycle.3. Plasma orexin-A levels increase as OSAHS becomes worse, therefore, it may be used as an important biological index to evaluate the severity of OSAHS.