Comparison Of Three Doses Of Dexamethasone In Glucocorticoid Receptor Expression, Inflammation, And Lung Injury In Septic Mice

Backgroung:The excessive inflammatory reaction caused by sepsis can eventually leading to the occurrence of multiple organ dysfunction,and lung is the most common target organ.Glucocorticoid(GC), as the most commonly clinical anti-inflammatory durgs, has been used for the adjuvant therapy of sepsis several years,but there are enormous controversial about it. In recent years, clinical studies have shown that low dose (about stress dose) GC is more effective than high dose GC.Our previous studies have shown that under stress dose can still raise the expression of the glucocorticoid receptor in lung tissue and reduce the lung damage caused by sepsis. To observe the effects of different doses of dexamethasone (Dex) on acute lung injury (ALI) in mice with septic shock,we conducted the study.Objective:To observe the effects of different doses of dexamethasone (Dex) on acute lung injury (ALI) in mice with septic shock and to investigate the possible mechanisms for such differences.Methods:Male Kunming mice were randomly divided into the following five groups: sham group, sepsis group, physiological dose Dex group, stress-dose Dex group and high-dose Dex group.We replicated the sepsis model using cecal ligation and puncture (CLP) method. After the operation, mice were given Dex0.12mg/kg (physiological dose Dex group),1.2mg/kg(stress dose Dex group) and12mg/kg(high-dose Dex group) intravenously, while the sham group and sepsis group were given the same volume of saline.24hours after treatment, histopathological changes of the lung were determined by HE staining. The expressions of glucocorticoid receptor (GR) and nuclear transcription factor κB(NF-κB) in lung tissues were investigated by immunohistochemical assays. The expressions of GR mRNA and NF-κB mRNA were detected by Real-time PCR. The expressions of TNF-a and IL-1β in the plasma were detected by ELISA.Results:①Compared with the sepsis group (9.35±1.39),the physiological dose Dex group(6.68±1.34)and the stress dose Dex group(7.71±1.27) had a lower grades of ALI pathologic changes(P<0.05).②Compared with the sepsis group(0.27±0.09), the expression of GR-a was increased in the physiological Dex group(0.37±0.07) and the stress dose group(0.35±0.08)(P<0.05).③The GR-a mRNA levels of physiological dose(2.80±1.01) and stress dose group(2.61±1.43) were higher than the sepsis group(1.66±0.97) and the high dose group(1.72±0.88)(P<0.05); Compared with the sepsis group, there was no difference in NF-κB mRNA levels among the Dex intervention groups(P>0.05).④The level of plasma TNF-α、IL-1β in the physiological dose Dex group and the stress Dex were lower than the sepsis group and the high dose group (P<0.05).Conclusion:In the sepsis mice model, the physiological dose Dex and the stress dose Dex could increase the level of GR-a, reduce lung injury and alleviate inflammation in lung tissue, which were much better than the high dose Dex.