Activation Of Nuclear Factor κB In Newborn Rats Sepsis

Objective: Up to now, sepsis is still an important disease that is harmful to newborn infants. The present studies have shown that in neonatal sepsis, there is a significant increase of tumor necrosis factor-α(TNF- α ), C-reactive protein(CRP), interleukins IL-6, IL-1β, IL-8. There have been some reports which suggest that the activated nuclear factor κB (NF- κB) can effect various cytokine by single or in coordination with other transcription factors by means of modulating the gene transcription of cytokine. The aim of the study is to explore the effect of NF-κB signal pathway in neonatal sepsis so as to provide the experimental base for corresponding clinical treatment of the sepsis, in which NF-κB is taken as the target.Methods: The sepsis model was made in newborn rats (10 days old) who were given staphylococcus aureus subcutaneously: (1) The electrophoretic mobility shift assay (EMSA) was used to observe the activity of NF- κB in the lungs and the livers in newborn rats with staphylococcus aureus sepsis. (2) Immunohistochemical method was used to observe the activity of NF- κB P65 in newborn rats with staphylococcus aureus sepsis. (3)The anti-oxidant pyrrolidine dithiocarbamate (PDTC) was used to observe its effect on the activities of liver and lung NF- κB and on the activity of splenic NF- κB P65 in newborn rats with staphylococcus aureus sepsis.Results: In newborn rats with staphylococcus aureus sepsis, the activity of lung NF- κB was enhanced at the 1st hour and reached at peak at the 3rd hour; then, it was weakened gradually and at the 24th hour faded away. The activity of the liver NF- κB was also activated and peaked at the 4th hour;then, it was gradually weakened and at the 24th hour faded away. The positive expression of splenic NF- κB P65 began to be intensified at the 1st hour, peaked at the 3rd hour and showed insignificant differences at the 24th hour as compared with the sepsis group. PDTC had an inhibitive effect on the activities of liver NF-κB and lung NF- K B and on the positive expression of splenic NF-κB P65. The larger the dosage was used, the more intensified inhibitive effect could be obtained.Conclusions:1. In newborn rats with staphylococcus aureus sepsis, the NF-κB of lung, liver and spleen are activated, and all indicate a peak.2. The anti-oxidant PDTC can inhibit NF-κB activity in a dose-effect fashion in newborn rats with staphylococcus aureus sepsis.