ABSTRACT
Objective To establish the rat overlap syndrome (OS) model of intermittent hypoxia (IH) and emphyse-ma, explore the systematic and endothelial inflammation status, and observe the changes of endothelial progenitor cell (EPC) level in peripheral blood. Methods Sixty male Wistar rats were randomly divided into four groups:normal oxygen control group (A), IH group (B), emphysema group (C) and OS group (D). The rat model of emphysema was established by smoke ex-posure for 16 weeks. From the 13-week, pre-programmed intermittent hypoxia/re-oxygenation (IH/ROX) exposure was giv-en in the meantime of smoke exposure. After exposure, ELISA method was used to detect values of tumor necrosis factor al-pha (TNF-α) and interleukin (IL)-6 in plasma and in the endothelium of right common carotid artery. Real-time-PCR assay was used to analyze RhoA mRNA level in the endothelium of right common carotid artery. The percentage of intima-media thickness (IMT) in the all wall of right carotid artery (C-IMT%) was measured. Flow cytometry was used to detect EPC levels. Results The values of TNF-α, IL-6, RhoA mRNA and C-IMT%were significantly higher in D group than those of A, B and C groups (P<0.05). The EPC levels were significantly lower in D group than those of A, B and C groups (P<0.05). Con-clusion OS rats had more serious vascular endothelial injury than that of emphysema or IH rats. Meanwhile, the repair ca-pacity of EPC for endothelium was worse, which increased the risk of cardiovascular diseases.
ABSTRACT
To study the effect of different levels intermittent hypoxia on inflammatory cytokines and adipokines in a rat model. 160 male Wistar rats were divided into five groups, three groups with intermittent hypoxia (5% O2:IH-1 group;7. 5% O2: IH-2 group;10% O2: IH-3 group), continuous hypoxia group (10% O2, CH group);and the intermittent normal oxygen control group(IN). Before the exposure and at the second, fourth, sixth, and eighth week after the exposure, eight rats in each group were selected randomly with blood samples collected. Blood glucose was measured by glucose oxidase-peroxidase ( GOD-POD ) reagents, double sandwich enzyme-linked immunosorbent assay ( ELISA) was used to detect serum concentration of insulin, tumor necrosis factor alpha( TNF)-α, interleukin ( IL)-6, leptin, and adiponectin and adipocyte nuclear factor kappa B ( NF-κB) levels. In IH-1, IH-2, and IH-3 group, blood glucose, insulin, TNF-α, IL-6, leptin, and nuclear NF-κB in rats showed consecutive increment after exposure to intermittent hypoxia, and those findings in IH-1 group were higher than those in IH-2 and IH-3 group (P0. 05). These results demonstrate that intermittent hypoxia could activate NF-κB and result in extensive changes of proinflammatory cytokines and adipokines in the serum of rats. The release of pro-inflammatory cytokines and adipokines keeps pace with the degree of intermittent hypoxia.
ABSTRACT
Objective To study the effect of different degrees of intermittent hypoxia (IH) on inflammatory cytokines and adipokines in 3T3-L1 adipocytes. Methods An intermittent hypoxia/reoxygenation (IH/ROX) from obstructive sleep apnea (OSA) adipocyte model was established. 3T3-L1 adipocytes were divided into five groups, three IH groups (5% O2, 7.5%O2 and 10%O2, referred to as IH-1, IH-2 and IH-3), sustained hypoxia group (10%O2, CH) and the normal oxygen control group (21%O2, IN). ELISA method was used to detect values of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), leptin and adiponectin in cell supernatant. Western blot analysis was used to detect levels of hypoxia-inducible fac-tor-1α(HIF-1α) and glucose transporter-1 (Glut-1). RT-PCR assay was used to analyze HIF-1α, Glut-1, TNF-α, IL-6, leptin and adiponectin mRNA expression levels in adipocytes. Results The expression levels of TNF-α, IL-6 and leptin were significantly higher in IH and CH groups than those of IN group (P<0.05). The expression levels of TNF-α, IL-6 and leptin protein and leptin mRNA were significantly higher in IH-1 group than those of IH-2 and IH-3 groups (P<0.05). The adiponectin and its mRNA levels were significantly lower in IH and CH groups than those of IN group (P<0.05). The adipo-nectin level was significantly lower in IH-1 group than that of IH-2 and IH-3 groups (P<0.05). Conclusion These results demonstrate that IH is related to the extensive changes in the expression and release of inflammation-related adipokines in cultured adipocytes. IH from OSA may underlie the development of the inflammatory response in adipocytes, which is in-volved in insulin resistance in patients with OSA.