核因子κB抑制剂对大鼠胰腺移植再灌注损伤的保护作用

Protective effect of nuclear factor-kappa B inhibitor on reperfusion injury after pancreasticoduodenal transplantation in rats

目的:探讨大鼠胰腺移植后核因子κB(NF-κB)活化对炎性介质表达和中性粒细胞浸润集聚的影响。方法:建立大鼠胰腺移植和假手术模型,实验组供体胰腺保存在含有NF-κB抑制剂脯氨酸二硫代氨基甲酸酯(ProDTC)的UW液中,受体鼠于移植前15min腹腔注射ProDTC(15mg/kg),对照组供体胰腺仅保存在UW液中,受体鼠腹腔注射等量生理盐水。结果:正常肝组织中NF-κBp65含量为1.17±0.23,移植后3h对照组NF-κBp65达高峰为4.32±0.95;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;髓过氧化物酶(MPO)活性明显增高。应用ProDTC者,NF-κBp65含量、TNF-α、MIP-2、ICAM-1mRNA和蛋白表达量、MPO活性均降低(P<0.01)。ProDTC也显著降低淀粉酶(Amy)、脂肪酶(Lip)、湿量/干重(W/D)水平,和对照组相比差异显著(P<0.01)。结论:移植后NF-κB活化上调了TNF-α、MIP-2、ICAM-1表达,从而增加中性粒细胞浸润,通过ProDTC抑制NF-κB活化可以减轻胰腺缺血再灌注损伤。

Objeαive： To study the effeα of nuclear faαor-kappa B （NF-κB） aαivation on neutrophil accumulation and expressions of tumor necrosis faαor-α （TNF-α）, macrophage inflammatory protein-2 （MIP-2）, and intercellular adhesion molecule-1 （ICAM-1） in the pancreas after pancreasticoduodenal transplantation. Methods： The models of pancreaticoduodenal transplantation and sham operation were established in the Wistar rats, and the models of pancreaticoduodenal transplantation were divided into experiment group and control group. The recipient rats were introperitoneally injeαed with 15 mg/kg of proline dithiocarbamate （ProDTC） in experiment group and with equal amount of normal saline in control group 15 minutes before transplantation. The donor pancreases were kept in UW solution containing ProDTC in experiment group and UW solution alone in control group for 12 hours. Results： In control group, the level of NF-κB p65 reached the peak 3 hours after transplantation, and the expressions of TNF-α, MIP-2, and ICAM-1 and the aαivity of myeloperoxidase （MPO） significantly increased. In experiment group, the level of NF-κB p65, the expressions of TNF-α, MIP-2, and ICAM-1, and the aαivity of MPO significantly decreased （P 〈 0.01 ）. The levels of amylase, lipase, and wet-to-dry weight ratio in experiment group were all significantly lower than those in control group （P 〈 0. 01 ）. Conclusion： ProDTC proteαs against pancreatic reperfusion injury by inhibiting NF-κB aαivation and decreasing subsequent expressions of proinflammatory mediators.