Effects Of Ulinastatin On NF -κB Activity Of Polymorphonuclear Neutrophils,tnf-α And IL-8 In Children Undergoing Cardiopulmonary Bypass

Objective: As a non-physiological processes,blood direct contact with the non-biological surfaces of artificial devices,surgical trauma,organ ischemia-reperfusion, intraoperative body temperature changes and the rapid changes in hemodynamics,cardiopulmonary bypass can quickly start the inflammatory cascade reaction . NF-κB is a protein transcription and regulation factor, it exists in almost all cells, regulating the cytokines, growth factors, chemotatic factor, cell adhesion molecules and some of the health and disease genes. Therefore,studying how to inhibit NF-κB activation, reducing pro-inflammatory gene expression,and then reducing tissue damage and inflammatory response during cardiopulmonary bypass has great significance. Ulinastatin(UTI) is a typical Kuniz type of protease inhibitors, having a broad role in enzyme inhibition. UTI can inhibit the release of inflammatory mediators, prevent cytokine cascade reaction, inhibit leukocyte activation and excessive release of inflammatory mediators.This study will observe the effects of ulinastatin on the NF -κB activity of polymorphonuclear neutrophils,TNF-αand IL-8 expression in children undergoing cardiopulmonary bypass.Methods: Sixty congenital tetralogy of Fallot patients were randomly divided into 3 groups of 20 each, group U1 : UTI 10000U/kg , group U2 : UTI 20000U/kg,control group(group C).Four milliliter radial artery blood was abstracted after induction of anesthesia, 30 min after beginning of CPB, 30 min, 4 h and 24 h after CPB finish. PMN NF-κB activity,TNF-αand IL-8 expression was tested in ELISA. Alveolar-arterial blood oxygen difference[P(A-a)O2] and respiratory index(RI) were also recorded after induction of anesthesia,30 min,4 h and 24 h after CPB finish. The automatic recovery rate of heart beats after cardiac resuscitation was observed.The dosage of dopamine and adrenaline after procedure,duration of mechanical ventilation after procedure and ICU stay time were recorded ,too.Results: The value of PMN NF–κB activity showed a progressive rise 30 min after beginning of CPB,the peak value of PMN NF–κB activity was got 30 min after CPB,then it declined. But the value of PMN NF–κB activity 24 h after CPB finish was still higher than that before CPB(P < 0.05) . The PMN NF-κB activity in treatment group was lower than that in control group 30 min after beginning of CPB,30 min,4 h and 24 h after CPB finish(P < 0.05).And the PMN NF-κB activity in group U2 was lower than that in group U1 30min after beginning of CPB, 30 min and 4 h after CPB finish(P < 0.05). Expression of TNF-αand IL-8 showed a progressive rise in all groups after the begin of CPB,the peak value was got 30 min after CPB finish,then it declined. The TNF-αand IL-8 expression in treatment group was lower than that in control group 30 min and 4 h after CPB finish(P < 0.05). And the value in group U1 was higher than that in group U2 30 min after CPB finish(P< 0.05). There were significantly positive correlation among the activation of NF–κB, and serum level of TNF-αor IL-8 in both the ulinastatin group and control group(P< 0.05). [P(A-a)O2] and RI: 30min,4h post-CPB were significantly higher than that of pre-CPB(P < 0.05); the peak value was got 30min after CPB finish. The [P(A-a)O2] and RI in treatment group was lower than that in control group 30 min and 4 h after CPB finish(P < 0.05). And there is not statistically significant in group U1 and group U2 (P > 0.05). The dosage of dopamine after procedure was higher in control group than that in group U1 and group U2 (P < 0.05). The automatic recovery rate of heart beats was higher in treatment group than that in control group(P < 0.05). Duration of mechanical ventilation after procedure and ICU stay time was longer in control group than in treatment group,too(P < 0.05).Conclusions: Ulinastatin can reduce the activity of PMN NF-κB in children undergoing cardiopulmonary bypass and reduce the expression of TNF-αand IL-8 . Ulinastatin can inhibit inflammatory reaction during CPB,shows positive myocardial protection and pulmonary protection,and the function of group U2 is better.