NF-κ Bp50基因缺失对小鼠实验性急性胰腺炎的影响

Role of NF-κB p50 protein in pathologic responses of experimental acute pancreatitis in mice

目的:实验诱导急性胰腺炎,观察p50基因敲除小鼠胰腺组织结构和功能的变化,探讨NF-κB在急性胰腺炎病理过程中的作用。方法:蛙皮素诱导建立野生小鼠和p50基因敲除小鼠的胰腺炎动物模型,检测各组小鼠p50、p65和cRel蛋白的表达情况,NF-κB DNA结合活性,血清淀粉酶和脂肪酶水平,胰腺组织的细胞坏死和凋亡情况和胰蛋白酶活性。结果:p50基因敲除小鼠缺乏p50蛋白表达,但p65和cRel蛋白代偿性增加。同野生型小鼠相比,p50基因敲除小鼠在发生急性胰腺炎时,NF-κB活性降低、细胞凋亡增加、细胞坏死减少,血清淀粉酶、脂肪酶和胰蛋白酶活性下降。结论:p50基因缺失后,NF-κB的其他亚单位蛋白表达代偿性增加;NF-κB对胰腺细胞坏死和凋亡有重要的调节作用,能减轻急性胰腺炎的病情。

Objective： To observe the roles of p50 protein in pathologic responses of cerulein （CR） pancreatitis in mice deficient in p50 protein of NF-κB. Methods： Pancreatitis was induced by i.p. injection of 50 μg/kg CR. The express and compensation of p65, p50 and cRel proteins of NF-κB ,NF-κB activity were measured using electromobility shift assay; parameters of pancreatitis, eg, amylase, lipase and trypsin were evaluated. The apoptosis , necrosis and caspase-3 activity were observed. Results： p50 knockout （KO） mice had no p50 protein expression and increased p65 and cRel proteins expression, p50 KO mice＇s NF-κB activity decreased and apoptosis increased in pancreatitis compared with wild type （WT） mice. There was no caspase-3 activition in both mice before and after pancreatitis. All KO mice had an increased necrosis and amylase, lipase, trypsin activity compared with WT mice in pancreatitis. Conclusions： The results indicated that NF-κB p50 genetic deletion might attenuate cerulean induced pancreatitis.