肿瘤坏死因子-α基因多态性对体外循环期心肌损伤的影响

Gene polymorphism of tumor necrosis factor-αaffecting severity of myocardial damage during cardiopulmonary bypass

目的探讨肿瘤坏死因子-α(TNF-α)基因G308A多态性对体外循环过程中心肌损伤的影响。方法63例先天性室间隔缺损(VSD)患者入选本研究,术前应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)的方法分析TNF-α基因-308位点多态性,并依此分为TNF1与TNF2两组。在打开与关闭右心房时取心房肌组织电镜观察并检测TNF-αmRNA表达。分别于麻醉诱导后(T1),体外循环转流20min(T2),体外循环结束时(T3),停机后6h(T4)抽血,放射免疫法检测血浆中TNF-α浓度。结果(1)两组患者的血浆中TNF-α浓度与心肌组织TNF-αmRNA在体外循环期均明显升高(P＜0．01)；(2)TNF2组心肌组织TNF-αmRNA表达明显高于TNF1组(P＜0．05),TNF2组术后24h心肌酶CK-MB明显高于TNF1组(P＜0．01),电镜观察TNF2组心肌组织损伤重于TNF1组(P＜0．05)；(3)在T2～T4时间点,TNF2组血浆中TNF-α浓度明显高于TNF1等位基因携带者(P＜0．05)。结论TNF-α基因G308A多态性可以影响体内TNF-α的转录与产生,并可能影响心肌损伤程度。

Objective To investigate the effect of polymorphism of TNF-α gene G308A on severity of myocardial damage during cardiopulmonary bypass （ CPB）. Methods Sixty-three congenital cases with ventricualr septal defect （VSD） were divided into groups TNF1 and TNF2 after TNF-α gene polymorphism was identified by polymerase chain reaction-restrlctlon fragment length polymorphism （ PCR- RFLP） before surgery. When the right atrium was opened and closed, specimens of myocardium were obtained to study the ultrastructural changes by electron microscope and determine expression of TNF-α mRNA. Concentration of TNF-α in plasma was measured by radio-immunity after anesthetic induction （T1） , 20 minutes of CPB （T2） , at the end of CPB （ T3 ） and six hours after CPB （T4） in all cases, respectively. Results （ 1 ）TNF-α level and the expression of TNF-α mRNA in myocardium were significantly increased during CPB （ P 〈 0.05 ） in both groups. （2） TNF-α mRNA level of group TNF2 was significantly higher than that of group TNF1 （P 〈0.05）. The myocardial CK-MB in group TNF2 was significantly higher than that in group TNF1 at 24 hours postoperatively （P 〈0.01 ）. The electron microscope showed more severe ultrastructural changes of myocardium in TNF2 group compared with that in group TNF1 （ P 〈 0.05 ）. （3）The concentration of TNF-α in blood plasma in group TNF2 was significantly higher than that in group TNFI at time points of T2-T4 （P 〈 0.05）. Conclusion Polymorphism of TNF-α gene G308A may influence the transcription and production of TNF-α in vivo and hence affect severity of myocardial damage.