[Expression of nuclear factor-kappa B and effect of pyrrolidine dithiocarbamate in Pseudomonas aeruginosa pneumonia rat model]

Abstract

Objective: To investigate the expression of nuclear factor-kappa B (NF-kappaB) and cytokines in Pseudomonas aeruginosa (PA)-induced pneumonia of rats, and the effect of pyrrolidine dithiocarbamate (PDTC).

Methods: Seventy-two male SD rats were divided into three groups at random:a control group, a PA group and a PDTC group (n = 24 each). The PA induced pneumonia model was established in SD rats. The rats of the control group and the PA group were intraperitoneally given saline (1 ml) at 60 min before PA exposure, while the rats of the PDTC group received the same volume of PDTC (200 mg/kg). After 60 min, the rats of the PA group and the PDTC group were intratracheally instilled with PA 0.2 ml (6 x 10(8) CFU/ml), while the rats of the control group received the same volume of saline. At 3 h, 6 h, 16 h, 24 h after PA exposure, the rats were examined. Then they were sacrificed and the lung were excised for routine histological analysis. Immunohistochemical staining with an antibody against activated NF-kappaB and Western blot were performed to detect the expression of NF-kappaB. The change of TNFalpha mRNA was identified by reverse transcriptase polymerase chain reaction (RT-PCR).

Results: Histological findings demonstrated that the lung exposed to PA showed significant changes in the lung structure, edema and pronounced inflammatory cell infiltration. Both symptoms and damages of the lung were less severe in the rats of PDTC group than those of the PA group. Compared with the PDTC group, the activation of NF-kappaB and the expression of TNFalpha in the PA group were significantly upregulated after PA challenge 3 - 24 h (P < 0.01), respectively; peak expression of NF-kappaB and TNFalpha were observed at 3 - 6 h after PA exposure.

Conclusions: The expression of NF-kappaB and TNFalpha induced by NF-kappaB play an important role in the pathogenesis of pneumonia. The inhibitor of NF-kappaB, PDTC, can relieve the lung damages produced by pneumonia.