[Effects of nuclear factor-kappaB on ventilator induced lung biotrauma by higher tidal volume and its interaction with pro-inflammatory cytokines].
OBJECTIVE
To investigate the changes of nuclear factor (NF)-kappaB 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-kappaB activity in nuclear protein from lung tissues was measured with electrophoretic mobility shift assay (EMSA); quantity of IkappaBalpha in cellular plasma from lung tissues was analyzed with Western blotting method; TNF-alpha 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-kappaB activity was higher in LMV than that in CMV and NMV groups (P < 0.01). Quantity of IkappaBalpha decreased progressively in LMV with time (P < 0.01) as compared to CMV and NMV. The expressions of TNF-alpha and IL-8 and their protein quantity in lung tissues significantly increased in LMV after ventilation compared to that in CMV and NMV (P < 0.01). The expression level of TNF-alpha reached its peak at 4 hrs and IL-8 at 6 hrs after ventilation then TNF-alpha 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
IkappaBalpha degradation and NF-kappaB activation were involved in modulating the expression of pro-inflammatory cytokines in lung tissues during the occurrence of lung injury caused by injuring MV.
Zhu
Jian-xing
JX
Department of Pediatrics, Xinhua Hospital, Shanghai Jiaotong University School of Medicine 200092, China.
Xie
Li-juan
LJ
Zhu
Xiao-dong
XD
Shen
Yi
Y
Chen
Fei
F
Shen
Xiao-ming
XM
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013990:Tidal Volume; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D055397:Ventilator-Induced Lung Injury / Q000378:metabolism*
D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha