吡咯烷二硫代氨基甲酸盐对大鼠急性坏死性胰腺炎肝损伤的保护作用

Protective effects of pyrrolidine dithiocarbamate on liver injury in rats with severe acute pancreatitis

目的:探讨核因子KB(NF-κB)抑制剂吡咯烷二硫代氨基甲酸盐(PDTC)对大鼠急性坏死性胰腺炎(ANP)的预防治疗作用。方法:大鼠80只随机分为正常对照组(Z)、胰腺炎组(Y)和干预纽.干预组又分为建模前1h PDTC干预组(A)、建模后1h PDTC干预组(B)和建模后6h干预组(C).干预组按不同时间ip PDTC.建模后6,12,24 h分批处死,临床全自动生化仪检测血清谷丙转氨酶(ALT)和淀粉酶(AMY),用凝胶迁移率改变分析法(EMSA)测定胰腺和肝脏中NF-κB的活性.同时观察胰腺和肝脏的病理改变.结果:正常大鼠组织中几乎测不到NF-κB的活性,与Z组比较,Y组胰腺和肝脏组织中6,12,24 h NF-κB活性分别明显增加(P<0.001).建模前1h,1h后使用PDTC,胰腺和肝脏组织中NF-κB活性均受到抑制(18.14±3.30,23.79±3.62 vs 24.82±4.57:10.68±2.51,13.83±2.70 vs 16.38±2.50;P<0.05),Y组血清ALT,AMY均高于对照组.病理学检查可以见到Y组和A,B,C组的胰腺和肝脏均有炎性改变,但A组较Y组明显为轻.结论:NF-κB的异常活化与SAP以及肝损伤有明显关系:PDTC对SAP时肝损伤的发生有一定的预防作用.

AIM： To investigate the relationship between nuclear factor-κB （NF-κB） activation and liver injury in rats with acute pancreatitis, and to assess the effectiveness of pyrrolidine dithiocarbamate （PDTC）, an inhibitor of NF-κB, on experimental acute necrotizing pancreatitis. METHODS： Sprague-Dawley rats were randomly divided into five groups： normal （Z）, pancreatitis （Y）, pre-intervention with intraperitoneal PDTC 1 h before modeling （A）; post-intervention 1 hour after modeling （B）; and PDTC 6 hours after modeling （C）. Each group was randomly sub-divided into 6-, 12- and 24- hour groups, respectively. An acute pancreatitis rat model was produced by injecting taurocholate into the biliopancreatic duct. Sub-groups were sacrificed at 6, 12 or 24 hours after modeling. NF-κB activ-ity in the pancreas and liver was examined by gel electrophoretic mobility shift assay. Levels of alanine aminotransferase （ALT） and amylase （AMY） were detected and pathological changes in liver and pancreas were observed. RESULTS： NF-κB binding activity was not detected in the Z group. At 6, 12, 24 hour, NF- κB activities of the pancreas and liver in the Y group were significantly higher than that in the Z group （P 〈 0.001）. One hour before and I hour after PDTC, PDTC could effectively inhibit NF- κB activity in the pancreas and liver （18.14 ± 3.30, 23.79 ± 3.62 vs 24.82 ± 4.57; 10.68 ± 2.51, 13.83 ± 2.70 vs 16.38 ± 2.50; P 〈 0.05）. NF-κB binding activity in the A group was more inhibited than that in groups Y or B. ALT and AMY were distinctly elevated in group Y. However there were no meaningful changes observed among groups A, B, C and Y. Phlogistic changes in the liver and pancreas could be observed in the Y group. After intervention with PDTC, pathological changes were significantly alleviated in group A. CONCLUSION： There are clear relationships between NF-κB and liver injury in severe necrotiz- ing pancreatitis. Early blockade of NF-κB activity may be effective for avoiding liver injury in acute necrotizing pancreatitis.