Abstract:

Objective  To observe the effects of dexamethasone(Dex) with different doses on acute lung injury in mice with septic shock. Methods  Ninety-two male Kunming mice were randomly divided into the following five groups: sham-operated group(n=12), sepsis group(n=20), Dex intervention groups(physiological-dose Dex group, stress-dose Dex group and high-dose Dex group， n=20 in every group). Sepsis models were replicated by cecal ligation and puncture method. 24 hours after the treatment, histopathological changes of the lung were determined by HE staining. The expressions of glucocorticoid receptor-α(GR-α) and nuclear transcription factor κB(NF-κB) proteins in lung tissues were investigated by immunohistochemical assays. The expressions of GR-α and NF-κB mRNA were detected by real-time PCR. The concentrations of TNF-α and IL-1β in the plasma were detected by ELISA. Results  ① Compared with sepsis group, physiological-dose Dex group and stress-dose Dex group showed lower grades of pathologic changes which indicated acute lung injury(all P＜0.05). ② Compared with sepsis group, the expression of GR-α protein increased in physiological-dose Dex group and stress-dose Dex group(all P＜0.05). ③ The GR-α mRNA levels of physiological-dose and stress-dose group were higher than sepsis group and high-dose Dex group(P＜0.05); There was no difference in NF-κB mRNA levels among Dex intervention groups and sepsis group (P＞0.05). ④ The levels of plasma TNF-α and IL-1β in physiological-dose Dex group and stress-dose Dex group were lower than those in sepsis group and high-dose Dex group(P＜0.05). Conclusion  In the sepsis mice model, both physiological and  stress dose of Dex can up-regulate the expression of GR-α, thus reduce lung injury and alleviate inflammation in the lung tissue, which were much better than high dose of Dex.

Key words: Sepsis; Acute lung injury; Dexamethasone; Glucocorticoid receptor-α; Nuclear factor kappa B