Obstructive sleep apnea (OSA) has been demonstrated to be
implicated in disorder of insulin secretion and diabetes mellitus.
In this study, we aimed to evaluate the protective role of tempol,
a powerful antioxidant, in chronic intermittent hypoxia
(IH)-induced pancreatic injury. The rat model of OSA was
established by IH exposure. The pathological changes, increased
blood-glucose level, and raised proinsulin/insulin ratio in
pancreatic tissues of rats received IH were effectively relieved
by tempol delivery. In addition, the enhanced levels of
pro-inflammatory cytokines, TNF-α, IL-1β, IL-6, and inflammatory
mediators, PGE2, cyclooxygenase-2 (COX-2), NO, and inducible
nitric oxide synthase (iNOS) in pancreatic tissue were suppressed
by tempol. Moreover, tempol inhibited IH-induced apoptosis in
pancreatic tissue as evidenced by upregulated Bcl-2 level, and
downregulated Bax and cleaved caspase-3 levels. Finally, the
abnormal activation of mitogen-activated protein kinase (MAPK)
and nuclear factor kappa-light-chain-enhancer of activated B cells
(NF-κB) signaling pathways induced by IH was restrained by
tempol administration. In summary, our study demonstrates that
tempol relieves IH-induced pancreatic injury by inhibiting
inflammatory response and apoptosis, which provides theoretical
basis for tempol as an effective treatment for OSA-induced
pancreatic injury.
Obstructive sleep apnoea syndrome (OSAS) is a common disorder associated with upper airway muscle dysfunction. Agents that improve respiratory muscle performance may have considerable therapeutic value. We examined the effects of acute exposure to sustained and intermittent hypoxia on rat pharyngeal dilator muscle function. Additionally, we sought to test the efficacy of antioxidant treatment in ameliorating or preventing hypoxia-related muscle dysfunction. Isometric contractile and endurance properties of isolated rat sternohyoid muscle bundles were examined at 35 °C in vitro. Muscle bundles were exposed to one of four gas treatments: hyperoxia (control), sustained hypoxia (SH), intermittent hypoxia (IH) or hypoxia/reoxygenation (HR), in the absence or presence of the superoxide scavenger – Tempol (10 mM). Stress-frequency relationship was determined in response to electrical stimulation (10-100 Hz in increments of 10-20 Hz, train duration: 300 ms). Muscle performance was also assessed during repetitive muscle stimulation (40 Hz, 300 ms every 2 s for 2.5 min). Compared to control, IH and HR treatments significantly decreased sternohyoid muscle force. The negative inotropic effect of the two gas protocols was similar, but both were of lesser magnitude than the effects of SH. SH, but not IH and HR, increased muscle fatigue. Tempol significantly increased sensitivity to stimulation in all muscle preparations and caused a leftward shift in the stressfrequency relationship of IH and SH treated muscles. Tempol did not ameliorate sternohyoid muscle fatigue during SH. We conclude that Tempol increases upper airway muscle sensitivity to stimulation but only modestly ameliorates respiratory muscle weakness during intermittent and sustained hypoxic conditions in vitro. Respiratory muscle fatigue during sustained hypoxia appears unrelated to oxidative stress., J. R. Skelly, ... [et al.]., and Obsahuje seznam literatury