[Potential molecular mechanism of multiple organ dysfunction syndrome induced by hemorrhage and endotoxin].
OBJECTIVE
To investigate the possible molecular mechanism of multiple organ dysfunction syndrome (MODS) associated with hemorrhagic shock followed by resuscitation and endotoxin.


METHODS
A rabbit model of MODS after hemorrhagic shock followed by resuscitation and endotoxin was used in this study. The expression of I-kappaB kinase-beta (IKK-beta), the activity of nuclear factor-kappaB (NF-kappaB) in macrophage (PAM) and Kupffer cell (KC), the concentration of tumor necrosis factor-alpha (TNF-alpha) in the culture supernatant were measured by in situ hybridization (ISH), electrophoretic mobility shift assay (EMSA) and enzyme linked immunoadsorbent assay (ELISA), respectively. Then the blood gas, biochemistrical and pathological changes in lungs, liver and intestines were examined in each groups.


RESULTS
In the MODS group, the expression of IKK-beta mRNA (0.15+/-0.03, 0.17+/-0.04), the activity of NF-kappaB (1.49+/-0.30, 1.72+/-0.36) and the levels of TNF-alpha[(279.74+/-25.91)ng/L, (300.05+/-30.86)ng/L] in PAM and KCs were significantly higher than those of normal controls[IKK-beta mRNA 0.03+/-0.01 and 0.02+/-0.01; NF-kappaB 0.25+/-0.06 and 0.31+/-0.10, TNF-alpha (137.33+/-6.09)ng/L and (134.85+/-12.09)ng/L, respectively, all P<0.01]. Also, the contents of blood urea nitrogen (BUN), alanine aminotransferase (ALT) in plasma significantly increased, the arterial oxygen partial pressure decreased, and the severity of organ damages in lungs, liver as well as intestines increased following MODS.


CONCLUSIONS
The IKK-beta expression, NF-kappaB activation and cytokine release may play important roles in the pathogenesis of acute lung injury and MODS.
Yin
Wen
W
Department of Emergency, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shanxi, China.
Hu
Xiao-min
XM
Yuan
Jing
J
Yang
Jian-hong
JH
Zhang
Jin-shan
JS
Pei
Jian-ming
JM
Luo
Yan-jun
YJ
D000818:Animals; D001784:Blood Gas Analysis; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004731:Endotoxins / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006470:Hemorrhage / Q000150:complications*; D051550:I-kappa B Kinase; D017403:In Situ Hybridization / Q000379:methods; D007728:Kupffer Cells / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D009102:Multiple Organ Failure / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011817:Rabbits; D012128:Respiratory Distress Syndrome / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004731:Endotoxins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase