RESUMO
Hyperoxic ventilation induces detrimental effects on the respiratory system, and ambient oxygen may be harmful unless compensated by physiological anti-oxidants, such as vitamin C. Here we investigate the changes in electrolyte transport of airway epithelium in mice exposed to normobaric hyperoxia and in gulonolacton oxidase knock-out (gulo[-/-]) mice without vitamin C (Vit-C) supplementation. Short-circuit current (Isc) of tracheal epithelium was measured using Ussing chamber technique. After confirming amiloride-sensitive Na+ absorption (DeltaIsc,amil), cAMP-dependent Cl- secretion (DeltaIsc,forsk) was induced by forskolin. To evaluate Ca2+-dependent Cl- secretion, ATP was applied to the luminal side (DeltaIsc,ATP). In mice exposed to 98% PO2 for 36 hr, DeltaIsc,forsk decreased, DeltaIsc,amil and DeltaIsc,ATP was not affected. In gulo(-/-) mice, both DeltaIsc,forsk and DeltaIsc,ATP decreased from three weeks after Vit-C deprivation, while both were unchanged with Vit-C supplementation. At the fourth week, tissue resistance and all electrolyte transport activities were decreased. An immunofluorescence study showed that the expression of cystic fibrosis conductance regulator (CFTR) was decreased in gulo(-/-) mice, whereas the expression of KCNQ1 K+ channel was preserved. Taken together, the CFTR-mediated Cl- secretion of airway epithelium is susceptible to oxidative stress, which suggests that supplementation of the antioxidant might be beneficial for the maintenance of airway surface liquid.
Assuntos
Animais , Camundongos , Deficiência de Ácido Ascórbico/metabolismo , Transporte Biológico/efeitos dos fármacos , Cloretos/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/antagonistas & inibidores , Colforsina/farmacologia , Oxigenoterapia Hiperbárica , Hiperóxia/fisiopatologia , Transporte de Íons/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Knockout/metabolismo , Camundongos Transgênicos , Microscopia de Fluorescência , Estresse Oxidativo , Oxigênio/efeitos adversos , Canais de Potássio/metabolismo , Mucosa Respiratória/efeitos dos fármacos , Sódio , Açúcares Ácidos/metabolismoRESUMO
AIM: To investigate the effects of berberine (Ber) on ion transport and hypersecretion induced by cholera toxin(ChT) in ileum and its mechanism. METHODS: Ussing Chamber technique was used to measure the potential difference(PD), short-circuit current(SCC), and the resistance(R) in isolated guinea-pig ileum. The effects of Ber on PD, SCC and R in glucose Tyrode solution or glucose-free Tyrode solution were examined. The secretory diarrhoea model was made by ChT to investigate the effects of ChT and ChT+Ber on PD, SCC and R. RESULTS: (1)The PD and SCC were decreased in glucose Tyrode solution by the Ber added in mocosal side or in serosal side in ileum of normal guinea-pig and which was with secretory diarrhoea ( P