NFκB抑制剂对白细胞介导肝脏缺血再灌注损伤的保护作用

Protective effects of NF-kappa B inhibitor on neutrophil-dependent ischemia/reperfusion liver injury in rats

目的 探讨大鼠肝脏缺血再灌注后核因子κB (NFκB)抑制剂对炎性介质表达和中性粒细胞浸润集聚的影响。方法 建立大鼠肝脏部分热缺血模型 ,实验组于缺血前 15min腹腔注射NFκB抑制剂脯氨酸二硫代氨基甲酸酯 (ProDTC 15mg/kg体重 ) ,对照组等量生理盐水注射。结果 再灌注 3h ,对照组NFκBP6 5达高峰 ,持续至 6h ;肿瘤坏死因子 α(TNF α)、巨噬细胞炎性蛋白 2(MIP 2 )、细胞间黏附分子 1(ICAM 1)mRNA表达和蛋白表达明显增强 ;再灌注 12h髓过氧化物酶(MPO)活性明显增高。应用ProDTC者 ,NFκBP6 5含量、TNF α、MIP 2、ICAM 1mRNA和蛋白表达量、MPO活性均降低 (P <0 0 5 )。再灌注 6hProDTC组也显著降低了天门冬氨酸转氨酶 (AST)、丙氨酸转氨酶 (ALT)、乳酸脱氢酶 (LDH)、W/D水平 ,和对照组相比差异显著 (P <0 0 5 )。结论 缺血再灌注后NFκB活化上调了炎性介质表达从而增加中性粒细胞浸润 。

Objective To investigate the effects of NF-kappa B (NFκB) inhibitor on expression of inflammatory media and infiltration of neutrophils after ischemia/reperfusion liver injury in rats. Methods The model of partial hepatic ischemia was established in Wistar rats. The rats were peritoneally injected with either prolien dithiocarbamates (ProDTC, 15 mgkg) or sterile saline in 15 min before the ischemia. Results In the untreated rats, the level of NFκB P65 obviously elevated at 1 h and peaked at about 3-6 h after reperfusion (RP). The transcription of TNF-α, MIP-2 and ICAM-1 and the release of serum TNF-α and MIP-2 significantly increased 3 h after RP. Capillary endothelial cells of the livers strongly expressed ICAM-1 12 h after RP. ProDTC treatment significantly decreased the content of NFκB P65 in the liver in concurrence with the expression of TNF-α, MIP-2 and ICAM-1 gene as well as the activity of myeloperoxidase (MPO) at the corresponding time points after RP (P<0.05). Administration of ProDTC resulted in a statistically significant decrease in AST, ALT, LDH and W/D (P<0.05). Conclusions ProDTC protects the liver from ischemia/reperfusion injury by suppressing NFκB activation and subsequent expression of proinflammatory mediators.