中国冶金工业医学杂志

N-乙酰半胱氨酸治疗大鼠急性坏死性胰腺炎作用机制的实验研究

作者：周文君张树友 ZHOU Wen-jun ZHANG Shu-you

单位：周文君 ZHOU Wen-jun(湘潭钢铁集团公司医院湖南湘潭 411101)张树友 ZHANG Shu-you(南华大学附属第二医院)

关键词：胰腺炎核转录因子-κB 细胞因子乙酰半胱氨酸

分类号：R576

出版年,卷(期):页码：2005,22(6):0-0

摘要：

目的:探讨N-乙酰半胱氨酸(NAC)对急性坏死性胰腺炎(ANP)胰腺腺泡细胞核转录因子-κB(NF-κB)、κB抑制蛋白(I-κB)活性以及血液中炎症细胞因子IL-6、TNF-α及ICAM-1含量的影响,揭示NAC治疗ANP的作用机制.方法:采用5%牛磺胆酸钠胰管逆行注射制备ANP动物模型.SD雄性大鼠60只,分为A、B、C三组,每组分4个时间点,每组每个时间点大鼠5只,采用随机分配原则分组.A组:假手术组,给予0.9%NS 0.3 ml/100 g;B组:ANP空白对照组,给予0.9%NS 0.3ml/100g;C组:NAC治疗组,给予0.075%NAC液0.3 ml/100 g.ANP后再继续分别观察1、3、5及7 h后采用颈椎脱位法处死大鼠,并立即取血、腹水、胰腺组织及肺组织供实验用.实验中采用免疫组化法(SABC法)观察胰腺腺泡细胞NF-κB活性和I-κB表达及酶联免疫法(ELISA)检测血液IL-6、TNF-α及ICAM-1含量.结果:NAC能够减轻ANP胰腺和肺组织损伤.SABC法显示抗NF-κB与NF-κB结合活性在3 h时B组较C组显著增强;而抗I-κB与I-κB结合活性强度在3 h时B组较C组显著减弱.ELISA法提示,呈点状出血坏死病理学改变的ANP血液中炎症细胞因子IL-6、TNF-α及ICAM-1在3 h即显著升高,5 h即达高峰,7 h又呈逐渐下降趋势,应用NAC治疗ANP后血液中炎症细胞因子IL-6、TNF-α及ICAM-1在3、5及7 h亦较ANP模型组显著降低.结论:(1)大鼠ANP胰腺腺泡细胞NF-κB活性增高,胰腺腺泡细胞胞质I-κB活性受到抑制,启动或促进控制炎症细胞因子IL-6、TNF-α及ICAM-1的基因转录,从而加重全身炎症反应.(2)NAC能抑制大鼠ANP胰腺腺泡细胞NF-κB活性,增强胰腺腺泡细胞胞质I-κB活性,抑制大鼠ANP血液中促炎因子的产生,减轻全身炎症反应.(3)NAC能明显改善大鼠ANP胰腺和肺组织损伤.

基金项目：

作者简介：

参考文献：

Wulexyn FG.Krappmann D.Scheidereit C The NF-κB/Rel and I-κB gene families: mediators of immune response and inflammation 1996 Bhatia M.Brady M.Shokuhi S Inflammatory mediators in acute pancreatitis 2000 Makarov SS NF-κappaB as a therapeutic target in chronic inflammation:recent advances 2000(11) Ichiyama T.Yoshitomi T.Nishikawa M NF-κB activation in peripheral blood monocytes/macrophages and T cells during acute Kawasaki disease 2001 Bierhaus A.Schiekofer S.Schwaninger M Diabetesassociated sustained activation of the transcription factor nuclear factor-κB 2001 Dunn JA.Li C.HRa T Therapeutic modification of nuclear factor κB binding activity and tumour necrosis factor-α gene expression during acute biliary pancreatitis 1997 Gukovsky I.Gukovskaya AS.Blinman TA Early NF-κappa B activation is associated with hormone-induced pancreatitis 1998(6) Satoh A.Shimosegava T.Fujita M Inhibition of nuclear factor-κB activation improves the survival of rats with taurocholate pancreatitis 1999 Dunn JA.Li C.Hra T Therapeutic modification of nuclear factor-κB binding activity and tumour necrosis factor-α gene ex pression during acute biliary pancreatitis 1997 Christopher S C.Omaima S.Kazuhiko F Diminished lung injury with vascular adhesion molecule-1 blockade in cholinedeficient ethionine diet-induced pancreatitis 2003 Ruffmann R.Wendel A GSH rescue by N-acetylcysteine 1991(18) Neurath MF.Becker C.Baebulescu K Role of NF-κappaB in immune and inflammatory response in the gut 1998

服务与反馈：

【文章下载】【加入收藏】