Intermittent hypoxia with or without hypercapnia is associated with tumorigenesis by decreasing the expression of brain derived neurotrophic factor and miR-34a in rats  

作　　者：Zhang Jing Guo Xu Shi Yanwei Ma Jing Wang Guangfa 

机构地区：[1]Department of Respiratory and Critical Care Medicine, PekingUniversity First Hospital, Beijing 100034, China [2]Department of Neurosurgery, Liaoning Cancer Hospital & Institute,Shenyang, Liaoning 110042, China [3]Department of RespiratoryMedicine, Peking University ShougangHospital, Beijing 100041, China

出　　处：《Chinese Medical Journal》2014年第1期43-47,共5页中华医学杂志（英文版）

基　　金：This study was supported by a grant from the National Natural Science Foundation of China （No. 81241004）.

摘　　要：Background Very recent studies revealed that obstructive sleep apnoea （OSA） is a contributor of the increased incidence and mortality of cancer in humans,but mechanisms of how OSA promotes tumorigenesis remains largely unknown.We investigated whether intermittent hypoxia with and without hypercapnia plays a role in tumorigenesis.Methods First,Sprague-Dawley （SD） male rats （12 weeks old） were subjected to different hypoxia exposures：intermittent hypoxia and intermittent hypoxia with hypercapnia; continuous hypoxia and normal air.The systemic application of chronic fast rate hypoxia with or without hypercapnia mimicked severe OSA patients with apnoea/hypopnea index equivalent to 60 events per hour.Then routine blood tests were performed and the levels of brain derived neurotrophic factor （BDNF） and miR-34a were examined.Results In contrast to intermittent hypoxia with hypercapnia,both intermittent hypoxia and continuous hypoxia treatments caused significantly higher levels of haematology parameters than normoxia treatments.Compared to normoxia,intermittent hypoxia with hypercapnia exposure resulted in substantial decrease of serum BDNF and,miR-34a in the lower brainstem,while less pronounced results were found in intermittent hypoxia and continuous hypoxia exposure.Conclusions The exposure of intermittent hypoxia with or without hypercapnia,mimicking the situations in severe OSA patients,was associated with,or even promoted tumorigenesis.Background Very recent studies revealed that obstructive sleep apnoea （OSA） is a contributor of the increased incidence and mortality of cancer in humans,but mechanisms of how OSA promotes tumorigenesis remains largely unknown.We investigated whether intermittent hypoxia with and without hypercapnia plays a role in tumorigenesis.Methods First,Sprague-Dawley （SD） male rats （12 weeks old） were subjected to different hypoxia exposures：intermittent hypoxia and intermittent hypoxia with hypercapnia; continuous hypoxia and normal air.The systemic application of chronic fast rate hypoxia with or without hypercapnia mimicked severe OSA patients with apnoea/hypopnea index equivalent to 60 events per hour.Then routine blood tests were performed and the levels of brain derived neurotrophic factor （BDNF） and miR-34a were examined.Results In contrast to intermittent hypoxia with hypercapnia,both intermittent hypoxia and continuous hypoxia treatments caused significantly higher levels of haematology parameters than normoxia treatments.Compared to normoxia,intermittent hypoxia with hypercapnia exposure resulted in substantial decrease of serum BDNF and,miR-34a in the lower brainstem,while less pronounced results were found in intermittent hypoxia and continuous hypoxia exposure.Conclusions The exposure of intermittent hypoxia with or without hypercapnia,mimicking the situations in severe OSA patients,was associated with,or even promoted tumorigenesis.

关 键 词：intermittent hypoxia HYPERCAPNIA sleep apnoea TUMORIGENESIS brain derived neurotrophic factor MIR-34A 

分 类 号：R730.2[医药卫生—肿瘤]