核因子-κB促使水肿型胰腺炎向坏死型胰腺炎转化  

Effect of NF-κB on gut-original endotoxemia converting edematous pancreatitis to necrotizing pancreatitis in mice

作　　者：吴丽颖[1] 王兴鹏[1] Adler G 

机构地区：[1]上海市第一人民医院,上海交通大学附属第一人民医院,上海200080 [2]德国乌尔姆大学

出　　处：《中华急诊医学杂志》2004年第2期82-84,i001,共4页Chinese Journal of Emergency Medicine

基　　金：上海市科委启明星课题资助 ( 99QB14 0 0 9);德国洪宝基金资助

摘　　要：目的　探讨核因子 κB (NF -κB)在肠源性内毒素血症促使急性水肿型胰腺炎 (AEP)向急性坏死型胰腺炎 (ANP)转化中的作用。方法　C5 7BL 6小鼠随机分 5组 :正常组 (n =5 )、脂多糖 (LPS)组(n =2 0 )、AEP组 (n =2 0 )、AEP +LPS组 (n =2 0 )、PDTC干预组 (AEP +LPS +PDTC)组 (n =2 0 )。腹腔内间隔 1h共 7次注射雨蛙素 (5 0 μg kg)诱导小鼠AEP。第 6h胃管内灌入LPS溶液 (5mg kg)。PDTC干预组于雨蛙素注射前腹腔内注射PDTC ,剂量为 10 0mg kg。监测 12h、 2 4h、 4 8h和 5d血清淀粉酶、乳酸脱氢酶 (LDH)活性 ;免疫组化观察胰组织Mac - 1(CD11b CD18)、E选择素、P选择素和ICAM - 1表达 ;Southern印迹检测胰组织TNF -α、IL - 1βmRNA变化。 结果　LPS单独并不引起胰组织明显病理变化和血清淀粉酶、LDH活性改变 ,但使小鼠AEP胰腺组织损伤加重 ,血清淀粉酶和LDH活性显著增加 ;胰腺组织Mac - 1表达增强 ;PDTC处理组血清淀粉酶和LDH活性显著降低 ,胰腺组织病理改善 ,细胞因子TNF -α、IL - 1βmRNA表达下调。 结论　肠源性内毒素血症可促使AEP转化为ANP。PDTC通过选择性抑制NF -κB阻断内毒素信号通路 ,抑制内毒素介导的高细胞因子反应及其继发的中性粒细胞活化 ,最终使胰腺炎程度减轻。提示NF -κB在肠源性?Objective To investigate the possible role of nuclear factor-kappa B(NF-κB)in gut-original endotoxemia converting acute edematous pancreatitis(AEP) to acute necrotizing pancreatitis(ANP)in mice, anti-oxidant pyrrolidine dithiocarbamate(PDTC)was applied in an attempt to inhibit the activity of NF-κB. Methods Eighty-five C57BL/6 mice were assigned to 5 groups randomly, including normal control,LPS, AEP, AEP plus LPS and AEP?LPS plus PDTC. AEP in mice was induced by the intraperitoneal injections of cerulein with a dosage of 50 μg/kg at hourly interval for seven times. LPS was administrated via a gastric tube with a dosage of 5 mg/kg at 6 h following the first cerulein or saline injection. PDTC was injected intraperitoneally at a dose of 100 mg/kg.Serum amylase and LDH activities were measured at 12 h,24 h,48 h and 5 d.Pathological alteration in pancreas was studied. Expressions of Mac-1 (CD11b/CD18), P-selectin, E-selectin and ICAM-1 were evaluated by using inmmunohistochemical procedures. Expressions of pancreatic cytokine genes were determined by means of Southern blotting.Results LPS alone didn't develop either morphological changes or biochemical alterations. Cerulein induced a typical changes of AEP in mice. Cerulein-induced AEP challenged by LPS could cause marked parenchymal necrosis and hemorrhage in pancreas, and significant increments of serum amylase and LDH activities. ANP in mice pretreated with PCTC resulted in amelioration of pancreatic histology and decline of serum amylase and LDH activities. Expressions of Mac-1, P-selectin, E-selectin and ICAM-1 in pancreas were weakened. Cytokine genes including TNF-α, IL-1β were also downregulated.Conclusion This study suggested that gut-original endotoxemia,which could not induce pancreatic injury per se,could transit AEP into ANP in mice.Over-stimulation of neutrophils and releasing of pro-inflammatory mediators would be contributing factors during this process.PDTC could reduce the severity of pacreatitis by inhibiting the activity of NF-κB,blockin

关 键 词：核因子-ΚB 水肿型胰腺炎 坏死型胰腺炎 肠源性内毒素血症 并发症 

分 类 号：R576[医药卫生—消化系统]