| BackgroundSepsis is defined as infection plus systemic manifestations of infection. Glucocorticoid (GC) has been used for treatment of sepsis for about fifty years. Clinical studies have proved that high-dose GC has no good in the treatment of sepsis and ARDS,but low dose,long course GC may improve the prognosis of ARDS patients.It has been found in septic anmial experiments that different doses GC have different effects on the expression of GR-a in the lung.But at present there is lack oftrials of impact of GC on GR in the kidney.ObjectiveObserving the impact of low dose hydrocortison on the pathalogical changes of kidey in septic rats, the expressions of Glucocorticoid receptor alpha(GR-a)and nuclear transcription factorκB(NF-κB) in the kidney and the evels of plasma TNF-a,IL-6,IL-1β,IL-10 to investigate the protective effect and mechanism of low dose Glucocorticoid(GC) on sepsis induced acute kidney injury(AKI).MethodsEighty healthy Wistar male rats were randomly divided into sham group(n=10),kidney injury group(n=35) and HC group(n=35).Septic acute kidney injury model was reproduced using cecum ligation and puncture(CLP) method. After the operation,observed the general conditions of rats and survival rate at 24th hour.15 survival rats were randomly choosen from AKI group and HC group.These rats were anesthetized to take IVC blood and both kidneys. Pathological changes of the kidney were detected by HE staining. The expressions of GR-a and NF-KB in the kidney were detected by immunohistochemistry.The expressions of IL-1β,IL-6,TNF-αand IL-10 in the plasma were detected by ELISA.Results1. The survival rates of each group24 hours after operation, all the rats in the sham group survived.15 rats survived in AKI group and 17 rats survived in HC group. The survival rates were 43%,49% respectively in AKI group and HC group.The survival rates showed no statistically significant (P>0.05)2. HE staining of renal structure observed under light microscopeThe renal structure in the sham group was near normal. Renal tubular epithelial cells swelling and loss,tubular brush border disappeared, tubular vacuolated in AKI group. Renal tubular epithelial cells slightly swelling, tubular slightly expanded in HC group.3.The results of immunohistochemistryCompared with the sham operation group,the expression of GR-a was decreased(P<0.05) and the expression of NF-κB was increased in HC group(P<0.01). Compared with AKI group,the expression of GR-a was increased and the expression of NF-κB was decreased in HC group(P<0.01);Compared with the sham operation group, the expression of GR-a was decreased and the expression of NF-κB was increased in AKI group(P<0.01).4. The results of ELISACompared with the sham operation group,the levels of plasma TNF-a,IL-6,IL-1β,IL-10 were increased in HC group (p<0.01). Compared with AKI group,the levels of TNF-a,IL-6,IL-1βwere reduced and the level of IL-10 was increased in HC group (p<0.01). Compared with the sham operation group, the levels of plasma TNF-a,IL-6,IL-1βwere increased (p<0.01) and the level of IL-10 was increased in AKI group (p<0.01)ConclusionsThe low dose hydrocortisone can inhibit the activity of NF-kB possibly by means of increasing the experssion of renal GR-a in septic rats. Accordingly reduce the production of inflammatory factors which participate in sepsis. So effectively inhibit the inflammation which happened in the sepsis and protect the renal injury in septic rats.. |
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