| Multiple organ failure (MOF) is the cause of 50% to 80% of all deaths in surgical ICUs, while the cause of which is still poorly understood and the treatment is still largely supportive now. A lot of reports point out that TNF may play an important role in the course of development of MODS. TNF requires cross-linking of cell-surface TNFR for signal transduction. So far there have not been reports on the researches that TNF-sTNFR-TNFR are closely kept in contact with the MODS model. In our study a new rat MODS model was successfully set up and, on the basis of the model, the deep and systemic studies on the relation between TNF and MOF, sTNFR:Fc effect on MOF were made. And the prevention and cure effects of the sTNFR:Fc and the machanism were also probed into. In part 1, a new rat MODS model was successfully set up with the complex factors of hemorrhagic shock and endoxin. Methods: 36 rats were randomly divided into three groups which were subjected to hemorrhagic shock+ re- suscitation + endotoxiemia group(group A,n 16),hemorrhagic shock + resu- scitation (group B,n=10) and endotoxiemia group C,nlO). By using hemo- spasia method, mean arterial pressure was decreased to 35-4Omml-lg for 1 hour. Then 60% of the letting blood and the double volume of equilibrium liquid were transfused back into the bodies for resuscitation. 12 hours later, 4.5mg/kg of endoxin (S. abortus equi) was given via vein. Results: 72 hours after the process, the SGPT,SGOT,Cr and BUN of group A were obviously increased and Pa02 was decreased significantly. Pathologically, changes were non?specific and were mainly inflammatory. The incidence of single organ failure in liver was 100%, in kidney 90%, in gastrointestinal tract 60% and in lung 40%.Conclusion:The rat MODS model can be successfully reconstructed by the use of double-hit. This model has high morbidity andhigh repetition, which was very simi1ar in a11 respects to the de1ayed twophase M0DS of human patients.In part 2, the protection effect of sTNFRp75: Fc on the tested anima1swas observed. Methods: 32 rats were random1y divided into two groups. M0Fmode1s were a11 reconstructed in two groups by the use of doub1e--hit. Inthe group B, sTNFRp75: Fc (0. 4mg/Kg) was administrated at the time of ear1ystage of resuscitation. Group A was given control treatment. The protoco1used to measure the presence of TNF cyto1ytic activity was by L929 ce11sas targets. The serum TNF Q 1eve1 were measured with ELISA. Resu1ts:Ingroup A, the 1eve1 of TNF bioactivity in plasma was up to a high 1eve1 aftershock and resuscitation and was decreased at l2 hour. After endotoxininjection, the 1eve1 of TNF Q rised again and the 1eve1 of TNF Q in secondpeak was higher than that in the first one. The amounts of TNF Q inununo-reactivity was simi1ar to the bioactivity 1eve1. There was significantinterre1ation-- ship between the leve1 of TNF Q and the morbidity of M0Fand the morta1ity. In contrast, TNF bioactivity was significant1y b1ockedby TNFR: Fc adminis-- tration and large amounts of TNF irnunoreactivity werepresent in TNFR: Fc group compared with M0DS models (p<0. 05). The symptoms,signs, and funct ions of the main organs were obviously improved in the groupB. The morbidity of M0F and the morta1ity were much 1ower in group B. Themorbidity of M0F in group A and group B was 100% and 43. 7% respective1y.The morta1ity in group A was 50% and in group B was 12. 5%. A significantdifference was present between the two groups. Conc1usion: TNFQ p1ays avery important ro1e in germinating and deve1oping of M0DS. The sTNFRp75:Fc has good safeguard effect on the anima1s of M0DS models. The resu1tsa1so suggest that serum TNF 1evels may not a1ways be a good indic... |
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