Adiponectin protects the genioglossus of rats against chronic intermittent hypoxia-induced injury via inhibition of endoplasmic reticulum stress

作者：Zhang Xiao-feng; Huang Han-peng; Ding Wen-xiao; Ding Ning; Lu Gan; Liu Jian-nan; Zhang Xi-long^*

来源：Chinese Medical Journal, 2013, 126(17): 3270-3275.

DOI：10.3760/cma.j.issn.0366-6999.20131660

• obstructive sleep apnea hypopnea syndrome
• intermittent hypoxia
• genioglossus
• endoplasmic reticulum stress
• adiponectin

Background 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.
Methods 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).
Results Significant hypoadiponectinennia 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 2 alpha (p-elF2 alpha), phosphorylated inositol-requiring transmembrane kinase/endoribonuclease la (p-IRE1 alpha), 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). ERS-associated 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 CIH-induced pathological changes in group C.
Conclusion Beyond hypoadiponectinemia, CIH could enhance ERS and induce activation of ERS-associated apoptotic pathways in genioglossus, which could be significantly improved by adiponectin supplement.

• 出版日期2013-9-5
• 单位江苏省省级机关医院; 南京医科大学