缺血预处理对再灌注心肌肿瘤坏死因子-α、白介素-6的影响

Effect of ischemic preconditioning on tumor necrosis factor-αand interleukin-6 in rabbits following myocardial ischemia and reperfusion

目的观察缺血预处理对家兔心肌缺血再灌注期(MIR)血清及心肌组织中肿瘤坏死因子-α(TNF-α)和白介素-6(IL-6)的影响,并探讨其心肌保护机制.方法24只家兔随机分为3组,每组8只:空白组(C组)、缺血再灌注组(IR组)和缺血预处理组(IP组).IP组阻断冠状动脉左前降支(LAD)5min,恢复血流10 min后,再行缺血30 min,再灌3 h;IR组仅单纯缺血30 min,再灌3 h;C组仅分离血管,不阻断血流.各组分别于缺血前5 min(I0)、缺血30 min(I1)、再灌注1 h(R1)和3 h(R2)取颈内静脉血,IP组于缺血5 min,再灌注10 min时(IP)加抽一次血样,3组实验结束取心肌组织,批量测定血清及心肌组织中TNF-α、IL-6浓度,光镜下观察心肌病理结构变化.结果IP组血清TNF-α于IP时点迅速增高(P＜0.01),I1～R2恢复至基值;IR组I1～R2增高,分别是I0的1.61、1.50倍.IP组血清IL-6在I1时有增高趋势,但无统计学意义(P＞0.05),R1、R2与I0比无变化;IR组于R1迅速增高,R1、R2分别是I0的1.56、1.74倍.IP组心肌TNF-α、IL-6高于C组(P＜0.01),显著低于IR组(P＜0.01).光镜下IP组心肌水肿与白细胞浸润程度较IR组明显减轻.结论IP对TNF-α、IL-6合成分泌的调控可能是IP保护再灌注心肌的又一个机制.

[Objective] To observe the effect of ischemic preconditioning on the production of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) following myocardial ischemia and reperfusion, and to investigate its mechanism. [Methods] Twenty-four rabbits were randomly divided into three groups: sham operation group (group C, n=8); ischemia reperfusion group (group IR, n=8) was subjected to a 30 min of left anterior descending coronary artery (LAD) occlusion followed by reperfusion for 3 h; ischemic preconditioning(group IP) was elicited by 5 min occlusion and 10 min reperfusion. TNF-α and IL-6 were measured at following points: 5 min before occlusion (I0), at the end of preconditioning ischemic period (IP), 30 min after occlusion (I1), 1 h (R1) and 3 h (R2) after reperfusion, cardiac homogenate. The pathological changes were investigated under light microscrope. [Results] In group IP, TNF-αincreased significantly at point IP (P <0.01), and dropped to baseline at I1~R2, IL-6 showed a tendency to increase at IP, though had no significance. In group IR, levels of TNF-α, IL-6 increased markly at I0, R1, and remained high during ischemia-reperfusion. Ischemic preconditioning decreased myocardial TNF-α, IL-6 (P <0.01 vs IR), however, higher than C (P <0.01). Under light microscope, mild myocardium edema and only a few inflammatory cells were found in group IP, While in group IR, the changes were more serious. [Conclusion] Preconditioning decreases serum and myocardial TNF-α, IL-6. Cardioprotection by IP is associated with reduced TNF-α and IL-6.