摘要
目的:探讨N-乙酰半胱氨酸(N-acetylcysteine,NAC)对大鼠重症急性胰腺炎(SAP)肝损伤的抑制作用机制.方法:54只SD大鼠随机分为假手术组(SO组)、胰腺炎组(SAP组)及NAC干预组(NAC组),各组18只.以4%牛磺胆酸钠溶液逆行注入胰胆管制作SAP模型.NAC组于造模后1h行股静脉注入NAC(200mg/kg).分别于3h、6h、12h时间点随机剖杀大鼠.采用SP免疫组织化学法检测肝组织NF-κB活性;利用逆转录-聚合酶链反应(RT-PCR)法检测肝组织iNOSmRNA表达;胰、肝组织行病理切片观察,同时行血清淀粉酶、肝功能(AST、ALT)检测.结果:SO组肝组织可见散在肝细胞NF-κB活化和iNOSmRNA低表达,SAP组NF-κB活化和iNOSmRNA高表达;NAC对肝组织NF-κB活性有抑制作用,降低iNOSmRNA表达,与SAP组比较差异显著(3h:0.32±0.05vs0.46±0.04,6h:0.56±0.07vs0.97±0.18,12h:0.87±0.14vs1.13±0.11,均P<0.05),并可降低血清淀粉酶、AST、ALT水平.结论:肝组织NF-κB活化及iNOSmRNA过度表达可能是SAP肝损伤发生的原因之一,NAC可抑制肝NF-κB活性及iNOSmRNA的表达对SAP肝损伤具有一定的抑制作用.
AIM：To explore whether N-acetylcysteine （NAC） reduces liver injury in rats with severe acute pancreatitis （SAP）.METHODS：Fifty-four Sprague-Dawley rats were randomized into sham-operation group,SAP group and NAC treatment group.SAP was induced in rats by retrograde injection of 4% sodium taurocholate into the pancreatic duct.Rats in the NAC treatment group received an intravenous injection of NAC （200 mg/kg） one hour after sodium taurocholate injection.All the animals were sacrificed at 3,6 and 12 h after SAP induction.The activation of nuclear factor-κB （NF-κB） in the liver was determined by immunohistochemistry.The hepatic expression of inducible nitric oxide synthase （iNOS） mRNA was assayed by reverse transcription-polymerase chain reaction （RT-PCR）.Meanwhile,plasma amylase and liver function （ALT and AST） were measured.RESULTS：SAP induction significantly enhanced NF-κB binding activity and up-regulated iNOS mRNA expression in the liver of rats.NAC treatment for different durations could significantly suppress the activation of NF-κB （3 h：0.32 ± 0.05 vs 0.46 ± 0.04,6 h：0.56 ± 0.07 vs 0.97 ± 0.18 and 12 h：0.87 ± 0.14 vs 1.13 ± 0.11,respectively;all P〈0.05） and reduce the levels of plasma amylase,ALT and AST.CONCLUSION：NF-κB activation and iNOS mRNA expression are associated with liver injury in SAP.NAC protects against SAP-induced liver injury perhaps by blocking the activation of NF-κB.
出处
《世界华人消化杂志》
CAS
北大核心
2010年第10期1046-1050,共5页
World Chinese Journal of Digestology
