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机构地区:[1]广东药学院临床医学系,广东广州501240 [2]合肥市第一人民医院消化内科,安徽合肥230061
出 处:《广东药学院学报》2004年第5期520-523,526,共5页Academic Journal of Guangdong College of Pharmacy
基 金:Thisworkwassupportedbyagrantfromnaturalsciencefoundationofthedepartmentofeducation,Guangdongprovince,China.(No.Z0 2 0 4 4)
摘 要: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NFObjective To demonstrate the effects and significance of blocked NF-κB activity with pretreatment of pyrrolidine dithiocarbamate (PDTC) or N-acetylcysteine (NAC). Methods Mouse acute pancreatitis was induced by injecting 20% L-arginine saline solution (2×2.0 mg/g body weight) intraperitoneally at 1 h interval. 1 h prior to L-arginine administrated intraperitoneally, 0.01 mg/g pyrrolidine dithiocarbamate (PDTC) or 0.1 mg/g N-acetylcysteine (NAC) was injected as pretreatment. Mice were respectively killed at various time following the second time L-arginine administration. NF-κB activity, IL-6 level, amylase activity in serum, wet/ dry quality ratio of the pancreas, and their histological structures were measured and observed. Results NF-κB obviously activated in pancreatitis induced by L-arginine. PDTC or NAC pretreatment markedly blocked NF-κB activation in pancreas and attenuated pancreatitis development. But there were no significant changes in serum amylase levels. Conclusions The results suggest that NF-κB activation is an important early event and the pretreatment of PDTC and NAC improves pancreatitis by blocking activity of NF-κB.
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