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目的探讨吡咯烷二硫氨基甲酸 (PDTC)和N -乙酰半胱氨酸 (NAC)在小鼠急性水肿性胰腺炎 (AEP)中对核因子 -κB(NF -κB)的DNA结合活性的抑制效应 ,并论证阻断NF -κB活性在AEP治疗中的可行性。方法 2 0 %L -精氨酸 (2× 2 .0mg/g体重 )腹腔注射诱导小鼠AEP ;空白对照组给予等量生理盐水。抑制剂PDTC或NAC组在造模前 1h腹腔内分别注射 0 .1mg/gPDTC、0 .1mg/gNAC。EMSA分析胰腺组织中NF -κB活性 ;碘比色法测定血清淀粉酶活力 ,放射免疫法测定血清IL - 6水平 ;留取胰腺组织分析病理形态学及湿干比值的变化 ;黄嘌呤氧化酶法测定胰腺组织SOD活力。结果L -精氨酸腹腔注射后 ,小鼠胰腺组织NF -κB活性较NS组明显升高。给予PDTC或NAC干预后 ,病变胰腺组织中NF -κB活性在 0 .5 ,3,6 ,12h四个时间点受到不同程度的抑制 ,并且伴随着血清IL - 6水平、胰腺组织学评分、湿干比值等指标的改善 ,但PDTC及NAC预处理对血清淀粉酶活力影响不大。结论NF -κB活化是L -精氨酸诱导的小鼠AEP早期的一个重要事件 ,PDTC或NAC可通过阻断NF -κB活性而抑制胰腺炎症的发展
Objective To investigate the inhibitory effect of pyrrolidine dithiocarbamate (PDTC) and N-acetylcysteine (NAC) on the DNA binding activity of nuclear factor-κB (NF-κB) in mouse acute edematous pancreatitis (AEP) Effect and demonstrate the feasibility of blocking NF-κB activity in AEP therapy. Method 2 AEP was induced in mice by intraperitoneal injection of 0% L - arginine (2 × 2.0 mg / g body weight), while the blank control group was given normal saline. The inhibitor PDTC or NAC group were intraperitoneally injected with 0.1 mg / g PDTC and 0.1 mg / g NAC respectively 1 h before modeling. EMSA was used to analyze the activity of NF-κB in pancreatic tissue; serum amylase activity was measured by iodometry; radioimmunoassay was used to detect serum IL-6; histopathology and wet / dry ratio were taken for analysis of pancreatic tissue; xanthine oxidase Determination of pancreatic tissue SOD activity. Results After intraperitoneal injection of L - arginine, the activity of NF - κB in mouse pancreatic tissue was significantly higher than that in NS group. After the intervention of PDTC or NAC, the activity of NF-κB in the diseased pancreas was inhibited to some extent at four time points of 0.5, 3, 6 and 12 h, and accompanied with the serum IL - 6 level, pancreatic histological score, wet Dry ratio and other indicators of improvement, but pretreatment of PDTC and NAC little effect on serum amylase activity. Conclusion NF-κB activation is an important event in L-arginine-induced early AEP in mice. PDTC or NAC can inhibit the development of pancreatic inflammation by blocking NF-κB activity