Effect of hydrocortisone on aquaporin-1 and Na-K-ATPase in rats with acute lung injury

Objective To investigate effects of hydrocortisone(HC) on Na-K-ATPase and aquaporin-1 (AQP-1) in rats with acute lung injury (ALI). Methods ALI model in early septic shock was induced by injection of Escherichia coli two times at 5 hours interval, with the first intraperitoneal injection of 6.50 ×10 10 cfu/kg and followed by an external jugular vein injection of 2.00×10 11 cfu/kg in Wistar rats. Forty animals were randomly divided into five groups: normal control (N), ALI without HC treatment (C), ALI treated with high dose of HC (150 mg/kg),medium dose(20 mg/kg) and ALI treated with low dose (6 mg/kg). Two hours after treatment, the lung samples were collected for histopathological examination and lung injury score. Expression of Na-K-ATPase, aquaporin-1 and glucocorticoid receptor (GR) in lung tissue was determined by immunohistochemical staining. Results The lung injury score (LIS) in the C group was significantly higher than that in the N group (P0.05). After administration of HC, LIS in the three HC treatment groups were significantly decreased compared with the C group (P0.05), and LIS in the low-dose HC group was the lowest (P0.05). The difference of LIS between high and medium-dose HC groups was not significant.The ratio of expression area of Na-K-ATPase and AQP-1 in the C group was significantly lower than that of N group (P0.05). After administration of HC, the ratio of expression of Na-K-ATPase and AQP-1 in three HC treatment groups were significantly increased compared with the C group (P0.05), and the ratio of expression of Na-K-ATPase and AQP-1 in the low-dose HC group was that of highest (P0.05). The difference of the ratio of expression area of Na-K-ATPase and AQP-1 between high and medium-dose HC groups being not significant; the ratio of expression of GR in the C group was significantly lower than that of the N group (P0.05). After administration of HC, the ratio of expression of GR in three HC treatment groups increased compared with the C group,and the ratio of expression of GR in the low-dose HC group reached significant difference (P0.05). The difference of the ratio of expression of GR between high and medium-dose HC groups was not significant. The expression of AQP-1, Na-K-ATPase and GR showed a significantly positive linear correlation(r=0.43,P=0.007;r=0.31,P=0.015). Conclusion Low-dose HC has the most remarkable effects on alleviating LIS and improving alveolar fluid transport. No dose-dependent effect of HC in the treatment of septic ALI is found. The difference in therapeutic effect produced by different doses of HC might be associated with the level of GR expression.