Objective:To investigate the expression of NF-κB (nuclear factor-κB) and PUMA(p53 upregulated modulator of apoptosis)in severe pancreatitis-acute lung injury(SAP-ALI) and the effect of proline dithiocarbamate (PDTC) therapy.
Methods:SD rats weighing 200-250g were randomly divided into three groups: Sham operation group(A group，n=24)，SAP-ALI group(B group，n=24),  SAP+PDTC treatment group(C group,n=24).The model of SAP was established by injecting 1ml/kg of 5% sodium taurocholate into the pancreatic capsule of the rats in B group. On the basis of B group, C group was treated by PDTC at 1h after modeling. Eight rats of each group were killed in the following 6,12 and 24 h. The histopathologic changes in lung and pancreas were observed. The expressions of NF-κB, PUMA and caspase-3 in the lungs were detected by Western blotting, the expressions of TNF-α、MIP-2 and ICAM-1 mRNA in the lungs were detected by RT-PCR. The pulmonary injury was determined by myeloperoxidase (MPO) activity and TUNEL detection.
Results:Pathologic scores of lung in B group (6-24 h)were significantly higher than those in A and C group (P<0.05).The expressions of NF-κB p65,PUMA,Caspase-3 and TNF-α,MIP-2,ICAM-1 mRNA in B group in differant time point（12,24 h） were all higher than those in A and C group(P<0.05). NF-κB was correlated strongly with PUMA （r=0.987, P<0.01）.Higher activity of MPO and caspase-3 active were seen in B group than that in  A and B group. DNA ladder was easily seen in group B.
Conclusions:PDTC treatment can inhibit apoptosis of alveolar epithelial cells in SAP-ALI by inhibiting the activation of NF-κB, by which  the PUMA was down-regulated, the bcl-2 was up-regulated and caspase-3 was down-regulated. On the other hand, PDTC can inhibit the activation of NF-κB,which in turn decreases the lung injury by inhibiion of the cytokine and inflammation medium.