The Protective Effect Of Different Doses Dexamethasone On Acute Kidney Injury Induced By Sepsis In Mice

Background:Sepsis is the systemic inflammatory response syndrome induced by infection. Acute kidney injury (AKI) caused by sepsis is one of the most common reasons which can increase the mortality of the patients. At present, the drug for AKI induced by sepsis is very little. Glucocorticoid (GC) as a kind of anti-inflammatory drugs, has been a adjuvant therapy of sepsis for decades, however, there has been controversial about its dose and efficacy. The clinical common dose is equivalent to the stress dose; some animal experiments show that glucocorticoid which is below the stress dose can also decrease the organ injury by sepsis. We did this study to compare the effects of different doses dexamethasone on acute kidney injury induced by sepsis.Objective:To investigate the effect of different doses of dexamethsone (DEX) on sepsis induced (AKI).Methods:130numbers of Healthy male Kunming mice are randomly divided into sham group, sepsis group, physiological dose DEX group, stress dose DEX group, high-dose DEX group. Each group except the sham group was performed with cecal ligation and puncture (CLP) method making the sepsis model. Oh and24h after CLP, mouse in physiological dose DEX group, stress dose DEX group and high-dose DEX group were given0.12mg/kg,1.2mg/kg,12mg/kg DEX intravenous respectively, while the same volume of physiological saline were given to the sham and sepsis group.24h and48h after CLP, mouse were killed to collect the plasma and kidney tissues, the histopathological changes of the kidney were determined by the HE staining, the expressions of GR-a in the kidney were detected by immunohistochemistry, The levels of GR-amRNA, NF-κB mRNA were detected by Real-time PCR, The levels of IL-1β and TNF-α in the plasma were detected by ELISA.Results:(1)The renal structure in the sham group was almost normal, renal tubular epithelial cells swelling, the loss of tubular brush border and vacuolization were evident, compared to the sepsis group, the pathological changes of renal tubular in physiological dose (p<0.01), stress dose group(p<0.01) and high dose group (p>0.05) all alleviated;(2)in24h and48h, the expressions of GR-α in physiological group are higher than the stress dose group(p<0.05) and the high dose group(p<0.01);(3) the GR-amRNA levels of physiological group are higher than the sepsis group and the high dose group(p<0.01,p<0.05), the GR-amRNA levels of physiological group are higher than the stress dose group in48h(p<0.05);the NF-κB mRNA levels of physiological dose and stress dose group were lower than the sepsis group and the high dose group(p<0.01,p<0.05), and there was no difference in NF-κB mRNA levels between the physiological dose and stress dose group;(4) compared to the sham group, the IL-1and TNF-α levels of the other groups were elevated(p<0.01), the IL-1and TNF-α levels of physiological dose and stress dose group were lower than the sepsis group and the high dose group(p<0.01).Conclusions:The physiological dose and stress dose DEX which can increase the GR-α levels of kidney and reduce the sepsis induced kidney injury are much better than the high dose DEX.