A Study On PMN NF-κB Activation And ICAM-1 Expression Induced By Cardiopulmonary Bypass And Interventional Effects Of Glutathione

Object: To investigate the nuclear factor-κB (NF-κB) activation and intercellular adhesion molecule-1 (ICAM-1) expression of polymorphonuclear neutrophil (PMN) during cardiopulmonary bypass (CPB), and to evaluate the interventional effects of reduced glutathione.Methods: 20 children with congenital heart diseases aged from 5 to 12 years were randomly divided into control group and interventional group. Patients in interventional group were applied reduced glutathione (30mg/kg). The blood was sampled at 6 time points, such as before operation, 20 minutes after CPB, rewarming, the end of CPB, 4 hours after operation, 24 hours after operation. PMN were isolated by centrifugation through discontinuous gradient percoll. PMN NF-κB activation was measured by EMSA. ICAM-1 expression was detected by immunohistochemistry. The adhensive rate of PMN to cultured endothelia cell was counted. The ultrastructure changes of PMN were observed by transmission electron microscope. The results in the two groups were compared statistically .Result:1. 20 minutes after bypass, PMN NF-κB had been activated in control group, peaked before rewarming, and returned to the nadir at 24 hours after operation. In interventional group, NF-κB activation was milder than that in the control group(P<0.05). 2. ICAM-1 expression on PMN was not found in early stage of CPB, became marked at rewarmming, and peaked at 4 hours after operation. The density of ICAM-1 expression in interventional group was far lower than that in control group at 4 h after operation(P<0.05).3. The adhensive rates of PMN to cultured EC increased significantly at 20 minutes after CPB (P<0.05,vs preoperation), and peaked at 4 hours after operation. The adhensiverates in interventional group were much less than those in control group at 4 hours after operation(P<0.05).4. Under EM observation, PMN and its nuclear size enlarged after CPB, with more pseudopodia formated. As well as,both low density and high density granules reduced. Mitochondria increased, some of which were swelling.Conclusions:CPB induced PMN nuclear factor-κB activation and ICAM-1 expression, and promoted the adhension of PMN to cultured EC. Priming with reduced glutathione inhibited PMN NF-κB activation and ICAM-1 expression, which implicated that reduced glutathione might benefit the amelioration of SIRS induced by CPB...