肿瘤坏死因子-α在心肌缺血预处理中的变化及其意义

Significance and changes of tumor necrosis factor-alpha in human myocardium ischemic preconditioning

目的 探讨缺血预处理（IP）对心肌细胞的保护机制.方法 在我院行瓣膜置换手术的患者36例,根据是否采取缺血预处理分为预处理组（20例）和对照组（16例）,比较两组炎症因子肿瘤坏死因子（TNF）-α和心肌细胞bcl-2、Caspase-3的变化,观察IP对机体炎症反应的影响.结果 两组患者细胞因子TNF-α均在主动脉开放6 h时达到高峰,术后5 d恢复到术前水平.预处理组开放后6 h、术后1 d、术后2 d TNF-α水平明显低于对照组（P＜0.05）.复灌后对照组心肌细胞bcl-2蛋白表达轻度提高,与阻断前比较差异无统计学意义;而复灌后IP组心肌细胞bcl-2蛋白表达明显提高,与阻断前和对照组比较,差异有统计学意义（P＜0.05）.对照组复灌后心肌细胞Caspase-3、TNF-α蛋白表达显著提高,IP组心肌细胞中Caspase-3、TNF-α蛋白表达也增高,但比对照组降低,两组间差异有统计学意义（P＜0.05）.术后2 d血清TNF-α与bcl-2呈负相关;术后2 d血清及开放后心肌TNF-α与Caspase-3有相关性.结论 缺血预处理可能通过降低机体的炎症反应途径达到心肌细胞保护的效果.

Objective To explore the mechanism of human myocardium protection after ischemia/reperfusion （I/R） injury by ischemic preconditioning. Methods Thirty-six patients undergoing valve replacement were divided into the ischemic preconditioning group （IP group, 20 cases） and non-ischemic preconditioning group （control group, 16 cases） according to whether they were given single cycle reperfusion before cardioplegia or not. Serum level of tumor necrosis factor-alpha （TNF-α） was measured with enzyme linked immunosorbent assay （ELISA）. The expression of myocardial bcl-2, Caspase-3 and TNF-α was detected. Results Serum TNF-α level was increased to the highest level on the 6th h after de-clamping and recovered to the normal level on the 5th day. On the 6th h, first day and second after de-clamping, serum TNF-α level was significantly lower in IP group than in control group （ P 〈0. 05 ）. The expression of myocardial bcl-2, Caspase-3 and TNF-α was increased in both groups after reperfusion, and bcl-2 was lower in control group than in IP group, but the levels of Caspase-3 and TNF-α were higher （ P 〈0. 05）. The expression of myocardial bcl-2 and Caspase-3 had a correlation with serum level of TNF-α on the second day after de-clamping. The expression of myocardial Caspase-3 also had a correlation with that of myocardial of TNF-α. Conclusion Ischemic preconditioning has the protective effect on human myocardial cells by decreasing systemic inflammatory response following ischemia reperfusion injury.