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The Protective Effects of Low-dose Hydrocortisone on Sepsis-induced Lung Injury in Rats Model is by Up-regulation Expression of the Glucocorticoid Receptor Alpha Isoform

Author: PengMiaoMiao
Tutor: WuDaZuo
School: Shandong University
Course: Department of Respiratory Medicine
Keywords: sepsis lung injury glucocorticoid receptor-α(GR-α) nuclear factor-κB (NF-κB) matrix metalloproteinase-9(MMP-9)
CLC: R459.7
Type: Master's thesis
Year: 2011
Downloads: 21
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Abstract

BackgroundSepsis is the main reason for acute lung injury/acute respiratory distress syndrome (ALI/ ARDS), glucocorticoid (GC) has been used for clinical treatment of sepsis dozens of years beacase of it’s significant anti-inflammatory effects,but there has been controversial about its exact mechanism,efficacy,dose and duration of treatment.Now widely recognized that high-dose GC has no good in the treatment of sepsis and ARDS,but low dose GC may improve the prognosis of ARDS and parts of septic shock patients.We speculate that different doses of GC may have different influence on the expression of GR-α/GR-β. This is partly can explain the different doses of GC produce different prognosis in ARDS patients.ObjectiveTO observe low-dose hydrocortisone’s influence on the expression of GR-α, nuclear factor-κB (NF-κB) and matrix metalloproteinase-9 (MMP-9), To explore the protective mechanism of low dose GC on eraly lung injury caused by sepsis.MethodsThe eighty healthy wistar male rats were randomly assigned to sham group(n=10),lung injury group(n=35) and HC group(n=35),then using cecum ligation and puncture(CLP) method to prepare the sepsis with lung injury model.After the operation observed the general condition and the survival rate after 24 hours.15 survival rats were randomly choosen from the lung injury group and HC group. Then the rats were killed to collect the lung, plasma specimen and arterial blood. Arterial blood gas and lactic acid analysis were taken immediately. The pathological changes of the lung tissue were detected by the HE staining. The GR-α、NF-KB、MMP-9 expression in the lung tissue were detected by immunohistochemistry method. The expression of IL-1βand IL-6 in the plasma were detected by ELISA.Results(1)The survival rates of each group:After 24h the 10 rats of sham group were all alive,the lung injury and HC group have 35 rats in each group,24h after the CLP operation,15 rats survived in in the lung injury group and the survival rate was 43%;in the HC group 17 rats survived and the survival rate was 49%.The mortality between the two group show no statistically significant.(2)The HC group and lung injury group have low level of PaCO2,PaCO2, and high level of lactic acid compared with the sham group(P<0.01), Compared with the lung injury group,the HC group have a high level of PaO2,PaCO2 (P<0.05)(3)The pathological changes of the lung were more serious in lung injury group than in HC group(P<0.01).(4)The results of immunohistochemistry method:Compared with the sham group,NF-κB,MMP-9were higher expressed in lung injury group and HC group(P<0.01), but GR-a was diminished expressed in the two groups (lung injury group P<0.01, HC group P>0.05); NF-κB and MMP-9 were higher expressed and GR-a was diminished expressed in lung injury group compared with the HC group(P<0.01).(5) The results of ELISA:Compared with the sham group, IL-1β、IL-6、TNF-a、IL-10 were higher expressed in lung injury group and HC group(P<0.01), IL-1β、IL-6、TNF-awere higher expressed and IL-10 was diminished expressed in lung injury group compared with the HC(6)The expression of GR-a was inversely correlated with NF-κB、MMP-9 and IL-1β、IL-6(P<0.01);the levels of NF-κB in the lung were positively correlated with MMP-9 and IL-1β、IL-6(P<0.01);the expression of MMP-9 was positively correlated with IL-1β、IL-6 in the plasma(P<0.01) ConclusionsThe protective effects of low-dose hydrocortisone on early acute lung injury resulting from sepsis is by up-regulating the expression of GR-a in the lung, and then restraining the inflammatory responses and excessive activation of the proteinase in the downstream.

The Protective Effects of Low-dose Hydrocortisone on Sepsis-induced Lung Injury in Rats Model is by Up-regulation Expression of the Glucocorticoid Receptor Alpha Isoform

Abstract

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