Relationship Between Intrapulmanary Expression Of NF-κB, Inflammatory Mediators And Lung Injury In Rats With Severe Acute Pancreatitis

Background: Despite considerable progress in understanding pathophysiology of pancreatitis, the mechanisms of the development of this diseases remain obscure. Over the past several years, evidence has been accumulating on the involvement of inflammatory mediators, such as cytokines-chemokines interleukin-1 (IL-1), IL-6, IL-8, tumor necrosis factor- a (TNF- a ), and platelet-activating factor (PAF), in the development of pancreatitis. Systemic levels of IL-6, IL-8 and TNF- a increase in patients with acute pancreatitis and correlate with the severity of the disease.A key regulator of cytokine induction is the pleiotropic transcription factor nuclear factor- K B(NF- κ B). NF- K B represents a family of proteins sharing the Rel homology domain, which bind to DNA as homo-or heterodimers, and activate a multitude of cellular stress-related and early response genes such as the genes for cytokines, growth factors, adhesion molecules, and acute phase proteins. NF- K B plays an important role in some severs inflammatory diseases and gastrointestinal tumors. Objective: To investigate the change in nuclear factor-KB (NF- κ B ) expression, the potential role of NF- K B in inflammation signal transduction and the relationship between its activation ,inflammatory mediators and lung injury in rats following sodium tauracholate-induced severe acute experimental pancreatitis ( SAP ) .Methods: One hundred and eight Sprague-Dawley(SD) rats were randomly divided into four groups: sham operation group ( SO), severe acute pancreatitis group ( SAP ), and severe acute pancreatitis treated with dexamethasone (DEX) group. The NF-κB expression of lung wasdetermined by immunohistochemical staining and the levels of serum amalase(AMS), tumor mecrosis factor- a (TNF- a ) and interleukin-6 (IL-6) were also detected, meanwhile, the pathological changes of pancreas and lungs were observed with light microscope. Results: In the SAP group, NF-κB in pulmanary tissue was expressed and the levels of TNF- a and IL-6 started increasing at 1 hour,, peaking at 3 hours and decreasing at 6 hours, while there was no marked expression in SO group (p<0.01). In DEX group ,the levels of serum TNF-a and IL-6 were significantly lower to that of SAP group , the expression of NF-κB were also significantly lower in DEX group than that in SAP group (p<0.05 ). The lung pathological changes were significantly alleviated in DEX group compared with SAP group (p<0.05). Conclusion: NF-κB is involved in the inflammation response of SAP and is specifically related with lung injury. Dexamethasone could effectively inhibit the expression of NF-κB , alleviate lung injury and regulate inflammatory mediators . NF-κB activation , systemic levels of IL-6 and TNF- a increase in with acute pancreatitis and correlate with the severity of the disease. NF-κB plays an important role in the development of severs acute pancreatitis.