Inflammatory Characteristics Of Emphysematous Rat Model With Sleep-related Hypoxemia

Objective and background:Sleep-related hypoxemia (SRH), which defined as "an oxyhemoglobin saturation (SpO2) during sleep of<90% for more than five minutes with a nadir of at least 85%" or">30% of total sleep time with an SpO2 of< 90%" in subject with a baseline awake SpO2 of≥90%" is common in patients with chronic obstructive pulmonary disease (COPD). About 27% of the patients with COPD have SRH, which can cause pulmonary hypertension, arrhythmia and sudden death. The pathophysiologic change of COPD is emphysema. Our objective is to establish a novo model of SRH in emphysema with rats, and explore the inflammatory status and inflammatory characteristics of this disease.Method:45 male Wistar rats were separated into 3 groups,15 per group, according to exposure conditions. The rats in Group A (SRH) were breed normally for 28 days. Since the 29th day, they were exposed to the mixed gas of 12.5% Oxygen for 3 hours during sleep time (9:00～17:00) every day (the hypoxia time was divided into 4 periods,45 min each); The rats in Group B (emphysema) were exposed to cigarette smoke twice every day (30min each time) for 56 days; The rats in Group C (emphysema with SRH) were exposed to cigarette smoke as the rats in Group B, and they were also exposed to mixed gas as group A since the 29th day. Continuous exposure for 56 days. Weight all the rats before and after the exposure, calculate the weight gains; time the swimming time at the 56th day. Then after anesthetization, we collected bronchoalveolar lavage fluid (BALF) for routine tests and obtained blocks of lungs, liver and pancreas for pathologic scoring and measurement of expression of IL-6mRNA of these tissues. Data were expressed as (x±s). Data were analyzed by SPSS 17.0 system. Group comparison was determined by one-factor analysis of variance. The comparison between each two groups was measured by SNK-q test. P value<0.05 denotes the presence of significant statistical difference.Result:(1) Weight gains and swimming time of Group B and C were lower than Group A, Group C was lower than Group B.The total cells sum, macrophage and lymphocyte of Group B and C were higher than Group A, Group C were higher than Group B. The lymphocyte ratio (%) of group B and C were higher than group A, group C was higher than group B.The rats in Group B and C manifested the histopathological features of emphysema. Pathological scores of lung and MLI of Group B and C were higher than Group A, Group C was higher than Group B. MAN of Group B and C were lower than Group A, Group C was lower than Group B.(2) The liver and pancreas from Group B and C manifested inflammatory cell infiltration (lymphocyte) and cellular swelling. Pathological scores of liver and pancreas of Group B and C were higher than Group A, Group C were higher than Group B. The IL-6/GAPDH of lung, liver and pancreas of Group B and C were higher than Group A, Group C were higher than Group B.Conclusion:The pathological changes of lung and blood gas analysis results confirmed that our emphysema rat model with SRH was successfully established. SRH aggravated emphysema and pathological injure of lung. The inflammatory characteristic of emphysema with SRH was lymphocyte infiltration, which was different from bacteria inflammatory status. That means, emphysema subjects can aggravate rapidly from SRH which resulted by emphysema itself, needing not the recurring of bacterial infection that traditionally considered as the only way through which emphysema develops.IL-6 is an important pro-inflammatory cytokine. IL-6mRNA was regulated by nuclear factor-KB (NF-κB). In patient with COPD, NF-κB was activated, expression of IL-6mRNA increased. Then, many inflammatory factors released and cause the systematic inflammation. While suffered from SRH, the expression of IL-6 mRNA of lungs, livers and pancreas increased, consumption increased, and motor ability decreased. That means SRH made the systematic inflammation more severe.All the results showed that the inflammatory damage of emphysematous rats with SRH was much more severe than SRH rats and emphysematous rats. SRH and emphysema had synergistic action in inflammatory damages. There is no similar animal model research in china or abroad.