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 

机构地区：[1]Department of Respiratory Diseases, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China [2]Department of Respiratory Diseases, Jiangsu Geriatric Hospital, Nanjing, Jiangsu 210024, China

出　　处：《Chinese Medical Journal》2013年第17期3270-3275,共6页中华医学杂志（英文版）

基　　金：This study was supported by grants from the National Natural Science Foundation of China （No. 81270145） and Clinical Respiratory Research Center of Jiangsu Province （BL2012012）.

摘　　要：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 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 2α （p-elF2α）, phosphorylated inositol-requiring transmembrane kinase/endoribonuclease 1α （p-IRE1α）, spliced X-Box binding protein 1 （XBPls） 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 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 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 2α （p-elF2α）, phosphorylated inositol-requiring transmembrane kinase/endoribonuclease 1α （p-IRE1α）, spliced X-Box binding protein 1 （XBPls） 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

关 键 词：obstructive sleep apnea hypopnea syndrome intermittent hypoxia GENIOGLOSSUS endoplasmic reticulum stress ADIPONECTIN 

分 类 号：R363[医药卫生—病理学]