The Study On Expression And Significance Of NF-κB In Preventing And Treating Multiple Organ Dysfunction Syndrome With High Volume Hemofiltration

Multiple organ dysfunction syndrome(MODS) is one of major reasons for the death of criticalpatients.For those unclear mechanisms,therapy effect is disappointed.Since Kramer firstly usedCAVH to treat severe acut renal failure in 1977s,the concept of continuous renal replacementtherapy (CRRT) have changed fundamentally within tewenty years. Accompanied With CRRTaccepted widely,investigation of MODS has gained extraordinary progression.Because the largeamount of inflammatory mediators are considered as the important cause of mortality in someMODS patients,most investigators think that the key of treating MODS is to remove highconcentration of middle and large molecular weight inflammatory mediators in bloodstream byultra-filtration and adsorption. Recently,investigators find that immune-disequilibrium is the mostimportant stage of MODS,so the best treating way is to rebuild immune-system-stabilization status.Continuous blood purification could weaken the peak concentration of pro-inflammatory andanti-inflammatory mediators,diminish inflammatory reaction and improve immunosuppressionstatus so as to rebuild the immune-system-stabilization status. NF-κB, as a key factor incomplicate signal transduction pathways, has been considered as an important factor in the processof MODS in recent research through modulating many inflammatory molecular such as TNFα,ICAM and COX. In this study, based on the pig MODS model,we used HVHF to prevent and treatMODS,through observing the expression and changes of NF-κB and cytokines in pre-andpro-HVHF, the influence of NF-κB on cytokines expression , we could find the valuable theoryevidence of HVHF in preventing and treating MODS. In the first part of the research a pig MODS model was set up successfully with the complexfactors of hemorrhagic shock and endotoxin. Methods: fifteen pigs were randomly divided into twogroups which were subjected to hemorrhagic shock plus resuscitation and endotoxiemia (group M,n=9), and normal group(groupC, n=6). In group M, by the hemospasia method, mean arterialpressure decreased to 45-55 mmHg for 1.5-2 hours. Then 60% of the let blood and the doublevolume of equilibrium liquid were transfused back into pigs for resuscitation,12 hours later,1.5mg/kg of endotoxin (Escherichia coli endotoxin E.colO111B4) was given via vein within24hrs.Heart and pulmonary function were monitored continuously, alive animals were sacrified in - 6 -第二军医大学博士学位论文 普通外科专业7th day. Blood samples were collected at every time points for serum ALT, AST, Cr, BUN andblood gas which were used to judge if MODS happened by comparing with themselves. Thepathomorphology changes of major organs were observed. Results :The results showed that ALT,AST, Cr and BUN of group M increased obviously and PaO2 decreased significantly during anobservation period of 168 hours. The incidence of single organ failure were 77.8% in lung, 66.7%in gastrointestinal tract,55.6% in liver, 33.3% in kidney and 22.2% in heart. The morbidity andmortality of MODS in group M were respectively 88.9% and 77.8%, much higher than the control.Conclusion:The MODS model could be successfully reproduced by use of double-hit,which hashigh morbidity and mortality, high repetition, features such as causative factors of injury,onset ofillness,clinical situation,diagnosis standard similar with those of clinical delayed two-phase MODS. The influence of HVHF on major organ function and cytokines was studied in the second part.Methods: nineteen pigs were randomly divided into two groups : MODS+HVHF group ( HF group ,n = 10) and MODS group without HVHF (M group , n = 9) . High volume hemofiltration wasperformed 1h after endotoxin finished,lasting 12h everyday,filters replaced daily,lasting 3 days.Heart and pulmonary function were monitored continuously, alive animals were sacrified in 7th day.Bloo...