Adiponectin alleviates contractile dysfunction of genioglossus in rats exposed to chronic intermittent hypoxia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Genioglossal dysfuntion takes an important role in pathogenesis of obstructive sleep apnea hypopnea syndrome (OSAHS) in which chronic intermittent hypoxia (CIH) is the major pathological origin. Recent studies have suggested genioglossal injury induced by CIH might be improved by adiponectin. The aim of this study was to investigate the effects of adiponectin on genioglossus contractile properties in rats exposed to CIH.</p><p><b>METHODS</b>Thirty-nine healthy male Wistar rats were randomly divided into three groups: normal control (NC), CIH and adiponectin supplement (CIH+Ad) with 13 rats in each. Rats in NC were kept breathing normal air, while rats in CIH and CIH+Ad experienced the same CIH environment eight hours per day for 35 successive days. Rats in CIH+Ad were given intravenous adiponectin of 10 µg twice a week for 30 successive days. Rats in the NC and CIH were injected with normal saline as a control. After 35 days' CIH exposure, the levels of serum adiponectin and genioglossus contractile properties were compared.</p><p><b>RESULTS</b>Serum adiponectin level was significantly lower in CIH than in NC (1210 ng/ml vs. 2236 ng/ml). Serum adiponectin level in CIH+Ad (1844 ng/ml) was significantly higher than CIH but lower than NC. Twitch tension, time to peak tension, half relaxation time and tetanic tension were significantly lower in CIH than NC and improved in CIH+Ad. All mean tetanic fatigue indices decreased more rapidly in the first 20 seconds than during the subsequent 100 seconds. Tetanic fatigue indices in NC and CIH+Ad were significantly higher compared to CIH.</p><p><b>CONCLUSIONS</b>CIH could lead to hypoadiponectinaemia, impaired genioglossus contractile properties and decreased fatigue resistance in rats. Such changes could be partially offset by supplementation of adiponectin.</p>

Adiponectin protects the genioglossus of rats against chronic intermittent hypoxia-induced injury via inhibition of endoplasmic reticulum stress / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Obstructive sleep apnea hypopnea syndrome, characterized by chronic intermittent hypoxia (CIH), is closely correlated with genioglossus dysfunction. CIH has been identified to mediate mitochondrial damage in genioglossus. It has been reported that endoplasmic reticulum stress (ERS) could be induced by mitochondrial dysfunction. This study aimed to investigate the role of ERS in CIH-induced genioglossus injury, as well as the possible intervention effect of adiponectin (Ad) supplement in rats.</p><p><b>METHODS</b>Forty-five male Wistar rats were randomly divided into three groups and submitted to room air (group A, n=15) as a control or CIH (groups B and C, n=15, respectively). Throughout the exposure period, intravenous Ad was given in group C; while intravenous normal saline was simultaneously given in groups A and B. After 35-day exposure, genioglossus samples were obtained from the pentobarbital-anaesthetized rats via surgical dissection, following blood sampling. Western blotting was applied to detect expressions of ERS signals and associated apoptotic pathways in genioglossus. Serum adiponectin levels were assessed via enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Significant hypoadiponectinemia was revealed in group B only (P < 0.05). Compared to those in groups A and C, expressions of markers involved in ERS, such as glucose regulated protein 78 (GRP78), p-PERK, phosphorylated eukaryotic initiation factor 2a (p-eIF2a), phosphorylated inositol-requiring transmembrane kinase/endoribonuclease 1a (p-IRE1a), spliced X-Box binding protein 1 (XBP1s) and activating transcription factor 6 (ATF6), were significantly enhanced in group B (all P < 0.01); while no significant difference was shown between groups A and C (all P > 0.05). ERSassociated apoptotic pathways were remarkably activated in group B. The involved markers detected as the expression of CCAAT/enhancer binding protein homologous protein (CHOP), B-cell lymphoma/leukemia associatied X protein (BAX) and caspase-12 were significantly elevated (all P < 0.01). Transvenous adiponectin supplement improved the above CIHinduced pathological changes in group C.</p><p><b>CONCLUSION</b>Beyond hypoadiponectinemia, CIH could enhance ERS and induce activation of ERS-associated apoptotic pathways in genioglossus, which could be significantly improved by adiponectin supplement.</p>

A preliminary study on correlation between adiponectin genotype polymorphisms and obstructive sleep apnea hypopnea syndrome / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Obstructive sleep apnea hypopnea syndrome (OSAHS) is regarded as a disease with strong genetic background and associated with hypoadiponectinemia. It is worthwhile to investigate the possible correlation between the single nucleotide polymorphisms (SNPs) in the adiponectin gene and OSAHS.</p><p><b>METHODS</b>With the TaqMan polymerase chain reaction (PCR) method, the SNPs at positions 45 and 276 in the adiponectin gene were determined in Chinese of Han nationality in Nanjing district consisting of 103 OSAHS patients (OSAHS group) and 67 normal controls (control group). The association of adiponectin genotype polymorphisms at positions 45 and 276 with OSAHS was analyzed.</p><p><b>RESULTS</b>No evidence of a direct association was found between OSAHS and adiponectin genotype SNP at positions 45 and 276 (P > 0.05). However, compared with those OSAHS patients having G/T + T/T genotype at position 276, the OSAHS patients with G/G genotype showed a longer neck circumference, a prolonged duration of the longest apnea event, and an elevated level of blood cholesterol and low-density lipoprotein cholesterol (P < 0.05).</p><p><b>CONCLUSIONS</b>No direct association was suggested between OSAHS and adiponectin genotype distribution at positions 45 and 276 in Chinese of Han nationality in Nanjing district. However, in OSAHS patients, those with adiponectin G/G genotype at position 276, seemed to have a higher potential risk in development of OSAHS than those having adiponectin SNP276 G/T + T/T genotype.</p>