Function Of NF-κB In MODSE And Delayed Xenograft Rejection

Nuclear factor-κ B(NF - κ B) is an ubiquitous transcription factor in mammalian cells which is responsible for immune reaction, inflammatory reaction, cell proliferation, apoptosis and other cell stress reactions.Mouse model for ageing and multiple organs dysfunction syndrome (MODS) were founded to explore the function of NF ?κ B in the processes of multiple organs dysfunction syndrome in elderly (MODSE). The expression and activity of NF ?κ B in these models were detected with immunohistochemistry and electrophoretic mobility shift assay (EMSA) respectively. The NF -κB activity increased remarkably in both models and the expression of NF -κB increased 17.9%, 11.9%, 59.4% in heart, liver and lung of aged mouse. In order to explore which genes play a key role in ageing processes, the proteomics changes of lung were studied between young and aged mouse with 2D electrophoresis and MALDI-TOF-MS and 11 proteins which had distinct expression were identified. We searched the protein database and 3 proteins were obtained. These proteins would benefit the research on ageing processes and might be targets to protect the MODSE. All the data suggested the mechanisms of MODSE might be that free radical accumulated in ageing processes and activited NF- κ B which promoted genes expession related to inflammation and then triggered the development of MODSE. The results from mouse model for MODS induced by zymosan appoved that NF- κ B indeed play an improtant role in MODS.In addition, NF-κB function in delayed xenografts rejection(DXR) were studied by transgenic engineering. Some data showed that activation of NF- κ B was the key point in DXR processes. A20 gene, which code for a zine-finger protein, were transfected into porcine arotic endothelial cells (PAEC) by lipofectimine. The results showed that A20 could inhibit the activation of NF- κ B and reduce the expression of E-selectin by 77.2%. We constructed another transgenic vector which contain the ElA gene and get 8 transgenic mice from 44 offsprings by microinjection. RT-PCR detection showed that Fl generation of 3 transgenic mice expressed the mRNA of ElA. Human serum was injected into Fl mice through caudal vein to induce the DXR and the expression of E-selectin on the surface of endothelial cells was detected by immunofluorecence. The results showed that the expression of E-selectin reducedremarkably in the liver, heart and kiney of transgenic mouse. All the data suggested A20 and El A gene transfection were helpful to overcome the DXR in xenotransplantaion.