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The Influence Of Extracorporeal Circulation On Th1/Th2, Tc1/Tc2 Differentiation And Transcription Regulatory Factors

Posted on:2007-09-11Degree:DoctorType:Dissertation
Country:ChinaCandidate:H F NiFull Text:PDF
GTID:1114360272961330Subject:Surgery
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Objection It has been displayed by statistic data that complications during extracorporeal circulation is related to the disorder of immune function,and there is little effective method to predict or prevent.To availably accommodate the immune function and maintain the internal balance is a thought to predict or prevent the complication.The biological effect of immune system can be divided into four aspect:inflammatory reaction, anti-inflammatory reaction,cell-mediated immunity,humoral-mediated immunity,which maintain balance through complicated internal association and is the precondition for self stabilization of body,but complications during extracorporeal circulation is also related closely to the imbalance of this system.Th1/Tc1 and Th2/Tc2 is important subgroup of T lymphocyte,which excrete various cytokines,accommodate immune response,has important contribution in transplantation immunity and tumoral immunity.Th1/Tc1 excretes inflammatory cytokines,such as IL-2,IFN-γ,TNF-α,which plays key role in cell-mediated immunity,anti-infection,organ-graft refection and autoimmune reaction. Th2/Tc2 excretes anti-inflammatory cytokines,such as IL-4,IL-5,IL-10,which has important contribution in humoral- mediated immunity and allergic response.So the regulat ion to cell differentiation has caused generally attention due to its conspicuous adjusted effect.The present research display that cytokines is the important agent during the Th1/Tc1 and Th2/Tc2 differentiation,but it only produce a marked effect on the early step, and the specificity transcription regulatory factor T-bet and GATA3 is the decisive internal agent to the differentiation of Th1/Tc1 and Th2/Tc2.To study the change of Th1/Tc1 and Th2/Tc2 subgroup and expression of the specificity transcription regulatory factor T-bet and GATA3,conduce to understand the etiopathogenesis and research new preventional method to complications during extracorporeal circulation.Method Based on above recognition,we observed the influence of extracorporeal circulation on the four aspect above-mentioned and functional subgroup of T lymphocyte, and the relationship between them.The research content is divided into three part:1.The influence of extracorporeal circulation on the morphous,metabolism and functional subgroup of T lymphocyte2.The influence of extracorporeal circulation to the immunological effect mediated by T lymphocyte.3.The status of T-bet,GATA3,STAT1 and STAT6 expression during extracorporeal circulation operation.Result:1.Comparing to preoperation,T lymphocyte in test group appears the feature of accrementition,such as increasing volume and kytoplasm,manifest vacuolus;Cell metaboilic level improves;The expressed level of IL-4mRNA and protein increases, but that of IFN-γdecreases.At the meantime,there is no obvious change in control group.2.Comparing to preoperation,extracorporeal circulation causes apoptosis of T lymphocyte improving,quantum of T lymphocyte decreasing;Occurrencing time of DTH delayed,degree suppressed;Ability to kill tumour cell breakdown;The marked change of immune globulin is not founded.At the meantime,there is no obvious change in control group.3.Comparing to preoperation,the expression of inflammatory medium IL-6 up-regulates temporally,while anti-inflammatory medium IL-10 does not change obviously in control group;In test group,extracorporeal circulation causes the up-regulation of anti-inflammatory medium IL-10 whose peak value precedes inflammatory medium IL-6;The peak value of IL-6 is still in 4h postoperation,but the expression level during operation and postoperation is lower to control group.4.Comparing to preoperation,the expression of specificity transcription regulatory factor T-bet and intranuclear expression of upstream transcription regulatory factor STAT1 to Th1/Tc1 down regulated,while the expression of specificity transcription regulatory factor GATA3 and intranuclear expression of upstream transcription regulatory factor STAT6 to Th2/Tc2 up regulated;At the meantime, there is no obvious change in control group. Conclusions:1.T lymphocyte appears accrementition reaction,the subgroup of Th1/Tc1 increases, but that of Th2/Tc2 decreases during extracorporeal circulation operation.2.Extracorporeal circulation has a depressant effect to cellular immune function, induces the expression of inflammatory medium IL-6 and anti-inflammatory medium IL-10 up-regulated temporally,while the expression level of IL-6 is depressed by IL-10;Cell differentiation of Th1/Th2 and Tc1/Tc2 not only objectively react these changes,but also has intimate relationship with them,which may be one of the internal mechanism.3.According to the change of Th1/Th2 and Tc1/Tc2,the expression of specificity transcription regulatory factor T-bet and intranuclear expression of upstream transcription regulatory factor STAT1 to Th1/Tc1 down regulated,while the expression of specificity transcription regulatory factor GATA3 and intranuclear expression of upstream transcription regulatory factor STAT6 to Th2/Tc2 up regulated during extracorporeal circulation operation;T-bet/GATA3 may be the decisive internal agent to the differentiation of Th1/Th2 and Tc1/Tc2,which may become a target to adjust the balance of Th1/Th2 and Tc1/Tc2,so as to accommodate the functional status of inflammatory and anti-inflammatory reaction,cellular immune and humoral immune.
Keywords/Search Tags:extracorporeal circulation, Complication, Inflammatory reaction, Anti-inflammatory reaction, Cellular immune, Humoral immune, Th1.Tc1, Th2.Tc2
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