Expressions Of Endothelin Receptors And Endothelin Converting Enzyme-1 In Pulmonary Hemorrhage In Newborn Rats

Obj ective To investigate the expressions of endothelin A receptor, endothelin B receptor, endothelin converting enzyme-1 in pulmonary tissue of Wistar newborn rats in different phases when developing pulmonary hemorrhage induce by low temperature-hypoxia/rewarming-reoxygenation.Methords 75 Wistar newborn rats are randomly divided into 5 groups: control group(n=15) and four experimental groups:low temperature group (n=15), hypoxia group (n=15), low temperature and hypoxia group (n=15), rewarming and reoxygenation group(n=15). Rats in normal group are exposed to normothermia and normoxia and, hypoxia group are exposed to hypoxia (FiO2 5-6%) for 6 hours, low temperature group are exposed to low temperature and normoxia (10±1℃, FiO221%) for 6 hours, low temperature and hypoxia group are exposed to hypothermia and hypoxia for 6 hours, rewarming and reoxygenation group are exposed to hypothermia and hypoxia for 6 hours and then to hyperthermia(37℃) and reoxygenation (FiO2>95%) for 2 hours. The gross anatomical and histological changes (HE staining) in lungs are observed. Expressions of endothelin A receptor(ETAR),endothelin B receptor(ETBR) and endothelin converting enzyme-1(ECE-1) are studied by immunohistochemistry method.Results (1)11 rats in experimental groups die while none in normal group and the mortality rate of experimental groups is 18.33%. Histological changes in experimenial groups include pulmonary alveoli and interstitial edema, septal fragmentation, pulmonary alveoli dilatation, fusion of pulmonary alveoli and pulmonary alveoli hemorrhage. (2) Expressions of ETAR increase significantly in low temperature group, hypoxia group, low temperature and hypoxia group comparing with normal group (P<0.05), and decrease significantly after rewarming and reoxygenation. There are no significant difference between normal group and rewarming and reoxygenation group (P>0.05). And there are no significant differenc between every two groups of low temperature, hypoxia, low temperature and hypoxia (all P>0.05). (3) Expressions of ETBR elevate significantly in all experimental groups comparing with control group (P<0.05) and there are no difference between every two experimental groups (all P>0.05).(4) Expressions of ECE-1 increase significantly in all experimental groups (P<0.05) but somewhat lower in rewarming-reoxygenation group and there are significant difference beteewn low temperature and hypoxia group and rewarming-reoxygenation group(P<0.05). No significant differenc could be found between every two groups of low temperature, hypoxia, low temperature and hypoxia (all P>0.05).Conclusion 1.Hypoxia, low temperature, low temperature-hypoxia and rewarming/reoxygenation are factors contributing to lung injury.2. Expressions of ETAR, ETBR and ECE-1 increase in groups of hypoxia, low temperature, low temperature-hypoxia which demonstrate that ETAR, ETBR and ECE-1 are relevant to pulmonary hemorrhage. ETAR and ECE-1 may contribute to pulmonary hemorrhage by enhancing biological function and promoting expressions of ET-1, respectively. Overexpressions of ETBR seem to be associated with self-protecting.