Role of nuclear transcription factor-κB in endotoxin-induced shock in rats

Abstract

To investigate the role of NF-κB in endotoxic shock in rats, the model of endotoxin-shock rats was induced by intravenous infusion of lipopolysaccharide (LPS). 1 h, 2 h, 4 h and 6 h after LPS injection, the activation of NF-κB in blood mononuclear cells and the content of TNF-α and IL-6 in plasma was detected by enzyme-linked immunoadsordent assay (ELISA). The level of mean arterial pressure (MAP) and the histopathological changes of lung and liver were also observed. The activation of NF-κB in mononuclear cells increased 1 h after LPS injection and reached its peak 2 h after the injection, and its level was higher than that of normal group. The level of TNF-α was increased 1 h after the infusion and peaked 2 h after the injection, and its level was higher than that of normal group after LPS infusion. The content of IL-6 increased gradually with time, the IL-6 level was higher than that of normal group after LPS injection. MAP was decreased gradually with time and its level was lower than that of normal group after LPS injection. Pathological examination showed that endotoxic shock could cause pulmonary alveolar hemorrhage, edema and infiltration of inflammatory cell in lung tissue and congestion, edema, capillary dilation and inflammatory cell infiltration in liver tissue. It is concluded that NF-κB can up-regulate the expression of TNF-α and IL-6 in plasma and play an important role in endotoxin-induced shock in rats.

Keywords

endotoxic shock / mononuclear cells / lipopolysaccharide / nuclear factor Kappa B / tumor necrosis factor-α / Interleukin-6 / mean arterial pressure

References

[1] LoY C, WangC C, ShenK P, et al. . Urgosedin inhibits hypotension, hypoglycemia, and pro-inflammatory mediators induced by lipopolysaccharide. J Cardiovasc Pharmacol, 2004, 44(3): 363-363

[2] HuZ J, SunL X, YongLi, et al. . The effect of continual hemofiltration on inflammatory mediators in endotoxic shock. Chin J Exp Surg, 2004, 21(6): 760-760

[3] AbrahamE. Nuclear Factor-κB and its role in sepsis-associated organ failure. J Infect Dis, 2003, 187(Suppl 2): 264-264

[4] TakumiT, YokoK, HirokoK, et al. . Effects of dexmedetomidine on mortality rate and inflammatory responses to endotoxin-induced shock in rats. Crit Care Med, 2004, 32(6): 1322-1322

[5] HubertB, FengQ, ThomasZ, et al. . Role of NF-κB in mortality of sepsis. Clin Invest, 1997, 100972-972

[6] RossL P, HelenF G, JatinderK D, et al. . Increased nuclear factor κB activation in critically ill patients who die. Crit Care Med, 2002, 281047-1047

[7] BlackwellT S, ChristmanJ W. The role of nuclear factor κB in cytokine gene regulation. Am J Respir Cell Mol Biol, 1997, 173-3

[8] KimP K, DeutschmanC S. Inflammatory responses and mediators. Surg Clin of North America, 2000, 80(3): 885-885

[9] BucovaM. Role of cytokines in the development of local and systemic inflammation and septic shock. Veitr Lek, 2002, 48755-755