Mechanism Underlying The Role Of NF-κB During The Inflammatory Injury In Emphysema With Intermittent Hypoxia In Rat Endothelial Cells

Objective: Chronic obstructive pulmonary disease(COPD)and obstructive sleep apnea(OSA)represent two of the most prevalent chronic respiratory disorders in clinical practice,the coexistence of OSA and COPD has been termed the “overlap syndrome”(OS).Patients with OS have a substantially greater risk of cardiovascular complications,morbidity and mortality,compared to those with either COPD or OSA alone.Therefore to improve the cognition and research the pathogenesis and system damage of OS,has important clinical value and social significance.To investigate mechanism underlying the role of nuclear factor Kappa B(NF-κB)which induced inflammatory injury and functional lesion of rat aortic endothelial cells in emphysema with intermittent hypoxia.Method:60 male Wistar rats were divided randomly into 4 experimental groups(n=15 each group): control group,emphysema group,intermittent hypoxia(IH)group,emphysema with intermittent hypoxia group.The rats in control group had ad libitum access to food and water under normal circumstance.The rats in the emphysema group were exposed to cigarette smoke twice one day(30min each time).As for intermittent hypoxia(IH)group,the rats were exposed to intermittent hypoxia circumstance(8h/day).Both cigarette smoke twice a day(30min each time)and intermittent hypoxia circumstance(8h/day)were imposed on the rats in emphysema with intermittent hypoxia group.All the rats were exposed for 8weeks.5 rats were randomly selected from each group to measure the blood gas eraly the ninth week.We collected lung and endothelial tissues of thoracic aorta from the rest sacrificed rats,and observed the pathological changes of lung tissue through HE staining.The levels of ET-1,TNF-α and IL-8 in rat endothelial tissues of thoracic aorta were measured by ELISA testing.Nitrate reductase was used to measure the levels of NO,and RT-PCR to detect the levels of NF-κB m RNA,ICAM-1m RNA,MMP-9 m RNA and e NOS m RNA.Results: Lung pathology and blood gas results showed that rat model of emphysema with intermittent hypoxia was established successfully.The levels of ET-1,TNF-α,IL-8 in emphysema with intermittent hypoxia group were 172.41±1.61ng/L,104.1±1.4 ng/L,272.1±3.6 ng/L respectively,significantly higher than control group,emphysema group and intermittent hypoxia group(all P<0.05).The level of NO was 27.07±0.57 μmol/L,which was significant reduced;The expression of NF-κB m RNA,ICAM-1 m RNA,MMP-9 m RNA in emphysema with intermittent hypoxia group was significantly upregulated compared with control goup,emphysema group and intermittent hypoxia group(all P<0.05).The levels of e NOS m RNA expression were significantly lower than other three groups.The expression of NF-κB m RNA was positively correlated with MMP-9 m RNA level(r=0.572,P<0.001)and the expression of NF-κB m RNA was negatively correlated with e NOS m RNA level(r=0.534,P<0.001);There was no statistical difference in levels of NF-κB m RNA and e NOS m RNA expression between intermittent hypoxia and emphysema group(P>0.05)Conclusion: Compared with simply emphysema or intermittent hypoxia exposure,inflammatory injury of aortic endothelial cells of rats induced by emphysema with intermittent hypoxia was even more serious,and may result in more serious cardiovascular complications.The activation of NF-κB channel may be an important mechanism of its inflammatory response.