DISORDERED BREATHING IN THE PERINATAL PERIOD INDUCES BONE AND METABOLIC INJURY

摘要

Disrupted breathing patterns subject the infant to repetitive exposure to nor-moxic followed by hypoxic conditions (i.e., intermittent hypoxia [IH]). Emerging evidence indicates that IH exposure exerts significant injury to IH-prone body systems. The extent of such injury is described poorly, despite the well-outlined prevalence of such breathing patterns in premature and post-natal infants. We examined in rat models how the incidence of perinatal IH influences adverse outcomes in long bones and the mandible. We treated post-natal day 0 (or PO) ~ P2 rat pups with IH for periods as short as one hour and then maintained the pups in normal ambient air. Tibia and mandibular hardness and elasticity significantly declined three weeks after IH exposure. Reduced mineralization and alkaline phosphatase appeared, in addition to other molecular changes (e.g., decreased collagen 1 and Runx2 expression in bone and in cultured osteoblasts treated under IH). Deficiencies also appeared in metabolic systems. Zinc levels declined in pancreatic beta cells, together with levels of the zinc uptake transporter (ZIP8), presumably from oxidative stress from IH. Disturbed zinc balance from diminished ZIP8 levels in pancreatic beta cells after IH challenge likely contributes to diabetogenic effects of increased blood glucose and decreased insulin levels, as well as disturbed glucose sensitivity. Exposure to IH through common appearances of disturbed breathing in the human neonate may exert similar consequences to the deleterious outcomes to bone density and pancreatic function found in these animal models.