Effects Of Tumor Necrosis Factor-α And Its Type Ⅱ Receptor Gene Polymorphisms On The Systemic Inflammatory Response Induced By Cardiopulmonary Bypass

Background:Systemic inflammatory response syndrome (SIRS) induced by cardiopulmonary bypass (CPB) is an important reason of postoperative complications. Tumor necrosis factor-α (TNF-a), a pro-inflammatory mediator, plays a pivotal role in the process. Excessive production of it can lead to organ dysfunction or even the death of the patient. TNF-a gene G308A polymorphism was observed to have an obvious effect on the production of TNF-a. Meanwhile, the signal transduction pathway, by which TNF-a activates nuclear factor-KB (NF-kB), is the base of cascade amplification of inflammatory reaction, in which TNF-a receptor II (TNFR II) produces a marked effect. TNFRII gene T196G polymorphism, which results in methionine(M) to arginine(R) substitution, can influence the stability of the membrane-bound receptor and may affect its combination with TNF-α and the activation of NF-kB accordingly. Thus it may influence the intensity of inflammatory reaction. Presently, there is no final conclusion that whether the polymorphism of TNF-α gene G308A could affect the production of TNF-a in vivo, corresponding research on its effect on SIRS induced by CPB is scarce, and whether the gene polymorphism of TNF-α and TNFRII affects the activation of NF-kB in polymorphonuclear neutrophils (PMN) during CPB is not clear yet.Objective:1. To observe the distribution of TNF-α G3O8A and TNFR II T196G gene polymorphisms in both healthy people and patients with congenital ventricular septal defect (VSD) in Chongqing;2. To investigate the effects of TNF-α G3O8A gene polymorphism on the serum concentration of TNF-a and the damage effects on myocardium during CPB;3. To investigate the effects of the combined gene polymorphism of TNF-a G308A and TNFR IIT196G on the activition of NF-kB in PMN during CPB.