人胰胆管合流异常胆汁对胆管细胞的影响及其机理探讨

Effect of Bile from Patients with Anomalous Pancreaticobiliary Ductal Union on Growth of Human Cells of Bile Duct

目的研究胰胆管合流异常(APBDU)患者的胆汁对人胆管细胞生长的影响,探讨APBDU与胆管癌发生的关系。方法应用四甲基偶氮唑蓝(MTT)比色法检测APBDU患者胆汁对胆管细胞增殖的影响,流式细胞仪测定其细胞周期分布及凋亡情况;Western blot法检测经APBDU胆汁处理的胆管细胞c-erbB-2蛋白表达水平的变化。结果APBDU患者胆汁与正常对照胆汁比较,能明显促进胆管细胞的增殖(P<0.05),这种促增殖作用可被环氧化酶COX-2抑制剂celecoxib或一氧化氮合成酶抑制剂L-NAME抑制;流式细胞仪分析经APBDU胆汁处理的胆管细胞其处于S期的细胞明显增多(P<0.001);Western blot法检测经APBDU胆汁处理的胆管细胞其c-erbB-2表达增多。结论APBDU患者的胆汁对正常胆管细胞增殖有促进作用,可能潜在致癌活性。

Objective To explore the effects of bile from anomalous parcreaticobiliary ductal union （APBDU） patients on the growth of hunan cells of bile ducts, and the relationship between APBDU with bile duct carcinoma. Methods Bile sample from APBDU patients and normal persons were used for cells of bile ducts. The proliferative effect of bile was measured by mathabenzthiazuron （MTT） assay; Cell cycle and apoptosis were analyzed by flow cytometry （FCM） ; Expression level of c-erbB-2 was detected by Western blot assay. Results Bile from APBDU pa tients significantly promoted the proliferation of human cells of bile ducts compared with normal bile （P〈 0. 05）. The effect was abolished by addition of COX-2 inhibitor or iNOS inhibitor. The percentage of S period cells in group pretreated with APBDU bile was significantly increased compared with pretreated with normal bile （P〈0. 001）. The expression level of c-erbB-2 was increased in cell pretreated with APBDU bile. Conclusion Bile from APBDU pa tients can promote the proliferation of normal cells of bile ducts and may have potential carcinogenesis.