核因子-κB在急性胰腺炎中的激活及NBD多肽的干预作用

Activation of nuclear factor-κB and intervention of NBD peptides in rats with severe acute pancreatitis

目的:探讨核因子-κB(nuclear factor-kappa B,NF-κB)及活性氧簇(reactive oxygen species,ROS)在大鼠SAP发病过程中的作用;并观察NF-κB必需调节蛋白结合域(NF-κB essentiamodifier binding domain,NBD)多肽对大鼠SAP的干预作用.方法:逆行胰胆管内注射50g/L牛磺胆酸钠(1mL/kg)制备大鼠SAP模型.大鼠64只,随机分成4组:假手术组,SAP组,TAT-NBD(WT)多肽组和TAT-NBD(MT)多肽组.术后6,12h处死大鼠,观察胰腺组织病理、血清淀粉酶和胰腺组织NF-κBP65蛋白的变化,检测胰腺组织MDA含量及T-SOD活力.结果:与假手术组比较,SAP模型组6,12h大鼠NF-κBP65蛋白表达显著升高(49.3±2.2 vs 4.3±1.4,65.8±1.8 vs 5.0±1.3,均P<0.05)MDA生成增加(212.7±12.5 vs 87.7±7.5296.8±13.3 vs 96.2±8.3,均P<0.05),T-SOD活力下降(88±10 vs 183±10,65±7 vs 194±10均P<0.05);与SAP模型组比较,TAT-NBD(WT多肽预处理6,12h后,NF-κBP65蛋白表达(25.9±2.3,38.9±2.6)显著降低(P<0.05),MDA生成(102.5±10.4,164.5±12.2)降低(P<0.05)T-SOD活力(153±11,168±12)增加(P<0.05)胰腺病理学评分下降(5.04±0.41 vs 8.71±0.45,5.45±0.34 vs 10.31±1.23,均P<0.05),淀粉酶无明显变化.TAT-NBD(MT)多肽组上述指标均无明显变化.结论:SAP时大鼠胰腺组织的NF-κB过度激活,活性氧簇生成增加;NBD多肽预处理可以抑制NF-κB过度活化,减少活性氧簇生成,减轻胰腺局部炎症损伤.

AIM： To study the role of nuclear factor-kappa B （NF-κB） and reactive oxygen species （ROS） in rats with severe acute pancreatitis （SAP）, and to evaluate the effect of NF-κB essential modifier binding domain （NBD） peptides on this model. METHODS： Sodium taurocholate （50 g/L, 1 mL/kg body weight） was retrogradely injected into rats＇ biliopancreatic ducts to induce the SAPmodel. Sixty-four rats were randomly divided into 4 groups： sham operation group, SAP group, TAT-NBD （WT） peptides group and TAT-NBD （MT） peptides group. The drugs were intraperitoneally injected into the rats 30 minutes before the operation. The changes of NF-κB P65 protein in pancreas, pancreatic histopathology, serum amylase, and malondialdehyde （MDA）, total- superoxide dismutase （T-SOD） in pancreas were evaluated 6 and 12 h after operation. RESULTS： In comparison with that in the sham operation group, the expression of NF-κB p65 protein was significantly enhanced in the SAP group at 6 or 12 h （49.3 ± 2.2 vs 4.3 ± 1.4, 65.8 ± 1.8 vs 5.0 ± 1.3, both P 〈 0.05）; the production of MDA was also increased （212.7 ± 12.5 vs 87.7 ± 7.5, 296.8 ± 13.3 vs 96.2 ± 8.3, both P 〈 0.05）; however, the activity of T-SOD was lowered （88 ± 10 vs 183 ± 10, 65 ± 7 vs 194 ± 10, both P 〈 0.05）. In comparison with that in the SAP group, the expression of NF-κB p65 protein （25.9 ± 2.3, 38.9 ± 2.6） or the production of MDA （102.5 ± 10.4, 164.5 ± 12.2） was markedly decreased in the TAT-NBD （WT） group, while the activity of T-SOD was notably increased （153 ± 11, 168 ± 12） （P 〈 0.05）; the histological scores for pancreas were also reduced （5.04 ± 0.41 vs 8.71 ± 0.45, 5.45 ± 0.34 vs 10.31 ± 1.23, both P 〈 0.05）; the level of serum amylase had no obvious change. The above indexes had no marked changes in the TAT-NBD （MT） group. CONCLUSION： NF-κB is over-activated and the production of ROS increases in SAP rats. NBD peptides could selectively inhibit the activation of NF-kappa B, the production of ROS, and thus lessen the inflammatory inury during SAP.