The Study Of Relationship Between Nuclear Transcription Factor-κB And Inflammatory Response To Cardiopulmonary Bypass

Objectives To investigate the changes of Nuclear Transcription Factor-κB(NF-κB) in Cardiopulmonary Bypass(CPB) and the effect on systemic inflammatory response and lung function by means of suppressing NF-κB. Methods 12 adult mongrels(weight 13 ± 1kg) were randomly divided into two groups, 6 for each group. Pyrrolidine dithiocarbamate(PDTC) that was the inhibitor of activation of NF-κB was administered via vein before operation in experimental group and saline was given in control group. Routine CPB was used in all animals. the technique of myocardium protection and ardiac arrest(cold crystalline cardioplegia) was same in both groups. the mean time of CPB was 105 mins in this model,nevertheless, aortic occlusion was strictly controlled about for 1 hour. NF-κB mRNA was measured by reverse transcription polymerase chain reaction(RT-PCR),lung samples were obtained 30 mins before CPB,30th min starting aortic clamping and 30 mins after CPB; Nuclear translocation of NF-κB was detected by Immunocytochemistry and immunohistochemistry StreptAvidin-Biotin Complex(SABC), peripheral venous blood and myocardium samples were taken 30 mins before and after CPB; Serum tumor necrosis factor ( TNF ) - α , interleukin(IL)-6,IL-8 were measured by enzyme-linked immunosorbent assays(ELISA), blood samples were received from the vein and sampling time was chosen as follows: a) 30 mins before CPB b) 30th min starting aortic occlusion c) 5 mins after CPB d) 60 mins after CPB e) 120 mins after CPB f) 240 mins after CPB; Lung biopsies were obtained 30 mins before and after CPB in both groups for microscope pathological examination. For statistical analysis, repeated-measures analysis of variance was used for multiple between-group comparisons. Results are expressed with F,P. P values ﹤ 0.01 were considered significant. Statistical analysis was performed using SAS 8.02. Results There was no significant difference in measured results before CPB between the two groups. The mRNA expression of NF-κB of lung tissue began to rise in both groups after CPB. But the increased production of NF-κB mRNA was significantly suppressed in experimental group compared with the control group(P﹤0.01).At the same time, nuclear translocation of NF-κB was greatly suppressed in these dogs receiving PDTC. Serum TNF-α,IL-6,IL-8 all increased significantly in both groups at 30th min starting aortic occlusion and 5,60,120,240 mins after CPB. The increased productions of TNF-α,IL-6,IL-8 were significantly suppressed in experimental group(P ﹤ 0.01). Lung tissue histologic examination revealed that in control group there were more obvious intraalveolar hemorrhage , leukocyte adhesion and interstitial edema compared with experimental group. Conclusion CPB can induce the mRNA expression and activation of NF-κB. PDTC can inhibit NF-κB activation and significantly attenuate inflammatory response after CPB, at same time protect the lung tissues.