Change Of Glucocorticoid Receptor Expression And Effects Of Ulinastatin On Septic Rat Lungs

Backgroung: Sepsis has become a major healthcare problem in ICU. The pathologic processe of it is still unknown, and the clinical therapy is also a big question. Recently, many researches suggest glucocorticoid receptor(GR) maybe play an important part in sepsis. In our previous research we found ulinastatin (UTI) had protective effects on septic rats. But now the relationship between UTI and GR is unknown.Objective:To investigate the change of GR expression and the effect of UTI on lungs of septic rat.Methods:We assigned healthy wistar male rats into three groups randomly: the sham group, the model group and the UTI treated group. The sepsis model was established by cecum ligation and puncture(CLP). After the operation the UTI group received an intravenous administration of 50 000u/kg at Oh and 12h, while the same amount of saline was given to the model group. The rats were killed to collect the lung and plasma specimen at the time points of 6h,12h and 24h. The expressions of TNF-α,IL-1β,IL-6 and IL-10 in the plasma were detected by ELISA. The pathological changes of the lung tissue were detected by the HE staining. Chemical colorimetry method was used to determine the level of MDA and SOD in the lung tissue. The protein expression of GR-αwas detected by immunohistochemistry method. The expressions of GR mRNA and NF-кB mRNA were detected by Real-time fluorescence quantitative PCR.Results:(1) Morphological examinations by HE staining showed that the pathological changes in pulmonary were improved in UTI group compared with that in model group, and the lung injury scores at 24h was significantly decreased (P《0.05).(2) TNF-α,IL-1β,IL-6 and IL-10 in the plasma were higher expressed in model group, compared with the control group (P<0.05 or P<0.01); at 24th hour after operation, the expression of each index in the UTI group was significantly lower than that in the model group (P<0.01).(3) Compared with the control group, the MDA levels in model group were increased while SOD decreased (P<0.01, P<0.05); in UTI group the levels of MDA were significantly lower than that of the model group at 12h and 24h while SOD higher (P<0.01).(4) The expression of GR-a in the lung tissues was the most in the control group among the three groups, in the model group it decreased with time; UTI can upregulate the expression of GR-a in the lung, and the level of GR-a was markedly increased in UTI 24h group compared with that of the model group (P<0.05).(5) The Real-time PCR results demonstrated that the expression of GR mRNA in the model group was significantly lower than that of the control group (P<0.01), and the GR mRNA level in UTI group of 24h was higher than that in model group (P<0.05).(6) Compared with the control group, the model group had a higher level of NF-кB mRNA at 24h (P<0.05). UTI can downregulate the level of NF-кB mRNA in model, and the NF-кB mRNA expression in UTI 24h group was statistical lower than that in the model group.Conclusions:The expression of GR in septic rat lungs is decreased. UTI can upregulate the expression of GR-a in the lung, and downregulate the level of NF-кB, TNF-a, IL-1, IL-6, IL-10, MDA and SOD. Therefore, our results suggest that GR play an important role in sepsis, and the protective effects of UTI on acute lung injury maybe occurred by regulating NF-кB signal pathways, restraining the inflammatory responses and inhibiting the oxidation stress, then up-regulating the expression of GR-a.