N-乙酰半胱氨酸对急性梗阻性化脓性胆管炎时内毒素性急性肝损伤的保护作用  

Protective effects of N-acetylcysteine against endotoxin-induced acute liver injury as a result of acute obstructive suppurative cholangitis in rat

作　　者：薛强[1] 刘作金[1] 杨慷[1] 涂兵[1] 丁雄[1] 

机构地区：[1]重庆医科大学附属第二医院肝胆外科,重庆400010

出　　处：《解放军医学杂志》2012年第6期610-613,共4页Medical Journal of Chinese People's Liberation Army

基　　金：重庆市医学科学技术研究项目(2010-2-156)~~

摘　　要：目的研究N-乙酰半胱氨酸(NAC)对大鼠急性梗阻性化脓性胆管炎(AOSC)时内毒素介导的急性肝损伤的保护作用及其机制。方法健康Wistar大鼠96只,随机均分为3组(n=32):急性胆管炎组(AOC组),结扎大鼠胆总管,于胆总管内注入大肠埃希菌O111:B4(菌落浓度5×1012cfu/L),建立急性AOSC动物模型;NAC预处理组(AOC+NAC组),建模前2h给予300mg/kg NAC预处理;胆总管结扎组(BDL组),仅结扎胆总管。3组动物分别于术后0、4、8、16h活杀取材(每组每时间点8只),检测肝组织中脂多糖(LPS)受体CD14及NF-κB蛋白水平,测定血浆LPS、TNF-α、丙氨酸转氨酶(ALT)和总胆红素(TB)水平,光镜观察肝组织病理学变化。结果随病程延长,AOC组血浆LPS、TNF-α、ALT、TB水平逐渐增高,肝细胞变性、坏死等病理改变逐渐加重,而肝组织中CD14和NF-κB蛋白表达显著增加。AOC+NAC组各时间点肝组织中CD14和NF-κB蛋白表达,血浆LPS、TNF-α、ALT、TB水平及肝组织病理学改变均低于AOC组(P<0.01)。结论 AOSC时内毒素介导的急性肝损伤与肝组织CD14、NF-κB表达上调有关。NAC预处理可通过抑制CD14表达及NF-κB活化而减轻AOSC时内毒素介导的急性肝损伤。Objective To study the protective effect of N-acetylcysteine（NAC） on endotoxin-induced acute liver injury as a result of acute obstructive suppurative cholangitis（AOSC） and its underlying mechanism in rat.Methods Wistar rats were randomly assigned into 3 groups： AOC group,the common bile duct（CBD） was ligated and 0.2ml of E.coli O111：B4 suspension（5×1012cfu/l） was injected into the bile duct to induce AOSC;AOC＋NAC group,pretreated with NAC（300mg/kg） 2h before the reproduction of AOSC;BDL group（control）,only the CBD was ligated.At 0h,4h,8h and 16h after CBD ligation,the levels of plasma endotoxin,TNF-α,alanine transaminase（ALT） and total bilirubin（TB）,CD14 and nuclear transcription factor-κB（NFκB） expressions of protein in liver tissue were assayed respectively.Pathological changes in liver tissue were examined with light microscope.Results With the prolongation of AOSC,the plasma endotoxin concentration was progressively increased,resulting in obvious elevation of TNF-α levels,and significant liver injury was provoked.These changes were characterized by progressive hepatic cell degeneration,increase in ALT and TB levels,with marked upregulation of the CD14 and NF-κB protein expressions.Compared with AOC group,the parameters such as plasma ALT,TB and TNF-α levels,CD14 and NF-κB protein expressions and hepatic histopathological injury decreased significantly in AOC＋NAC group（P0.01）.Conclusions Endotoxin-induced acute liver injury is related to a progressive upregulation of expression of CD14 and NF-κB in liver tissue during AOSC.NAC may attenuate the endotoxin-induced acute liver injury by down-regulating CD14,NF-κB expression and inhibiting over-activation of Kupffer cells（KCs）.

关 键 词：乙酰半胱氨酸 胆管炎 脂多糖类 抗原 CD14 NF-κB 枯否细胞 

分 类 号：R575.7[医药卫生—消化系统]