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《Chinese Journal of Pediatrics》 2006-04
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Effects of nuclear factor-κB on ventilator induced lung biotrauma by higher tidal volume and its interaction with pro-inflammatory cytokines

ZHU Jian-xing,XIE Li-juan,ZHU Xiao-dong, SHEN Yi,CHEN Fei,SHEN Xiao-ming. Department of Pediatrics, Xinhua Hospital, Shanghai Jiaotong University School of Medicine 200092,China  
Objectives To investigate the changes of nuclear factor (NF)-κB activation in lung tissues and expression of cytokines in homogenate from lung tissues in infant rabbits with mechanical ventilation (MV) caused lung injury.Methods Forty-five general grade healthy infant rabbits were randomly divided into 3 groups: (1) Control: with no MV (NMV, n=9); (2):Conventional MV (CMV, n=9): VT=8 ml/kg; (3): MV with large tidal volume (VT) (LMV, n=9), VT=24 ml/kg. NF-κB activity in nuclear protein from lung tissues was measured with electrophoretic mobility shift assay (EMSA); quantity of IκBα in cellular plasma from lung tissues was analyzed with Western blotting method; TNF-α and IL-8 mRNA and their concentrations in homogenate were measured from lung tissues with RT-PCR and ELISA, respectively.Results At all time points NF-κB activity was higher in LMV than that in CMV and NMV groups (P0.01). Quantity of IκBα decreased progressively in LMV with time (P0.01) as compared to CMV and NMV. The expressions of TNF-α and IL-8 and their protein quantity in lung tissues significantly increased in LMV after ventilation compared to that in CMV and NMV (P0.01). The expression level of TNF-α reached its peak at 4 hrs and IL-8 at 6 hrs after ventilation then TNF-α decreased significantly at 6 hrs after ventilation. Pathological examination of the lung tissues showed that as MV extended over the time in LMV, alveolar structures were severely destroyed and large number of WBC infiltrated in both alveolar sacs and pulmonary interstitia with RBC leakage. However, there was less lung injury in CMV and no obvious injury in NMV.Conclusions IκBα degradation and NF-κB activation were involved in modulating the expression of pro-inflammatory cytokines in lung tissues during the occurrence of lung injury caused by injuring MV.
【CateGory Index】: R363
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