CAJ | 학술논문

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20%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1 h腹腔内分别注射0.1 mg/g PDTC、0.1 mg/g NAC.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0.5,3,6,12 h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.
목적탐토필각완이류안기갑산(PDTC)화N-을선반광안산(NAC)재소서급성수종성이선염(AEP)중대핵인자-κB(NF-κB)적DNA결합활성적억제효응,병론증조단NF-κB활성재AEP치료중적가행성.방법20%L-정안산(2×2.0mg/g체중)복강주사유도소서AEP;공백대조조급여등량생리염수.억제제PDTC혹NAC조재조모전1 h복강내분별주사0.1 mg/g PDTC、0.1 mg/g NAC.EMSA분석이선조직중NF-κB활성;전비색법측정혈청정분매활력,방사면역법측정혈청IL-6수평:류취이선조직분석병리형태학급습간비치적변화;황표령양화매법측정이선조직SOD활력.결과L-정안산복강주사후,소서이선조직NF-κB활성교NS조명현승고.급여PDTC혹NAC간예후,병변이선조직중NF-κB활성재0.5,3,6,12 h사개시간점수도불동정도적억제,병차반수착혈청IL-6수평、이선조직학평분、습간비치등지표적개선,단PDTC급NAC예처리대혈청정분매활력영향불대.결론NF-κB활화시L-정안산유도적소서AEP조기적일개중요사건,PDTC혹NAC가통과조단NF-κB활성이억제이선염증적발전.
Objective 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.