解放军医学杂志2012,Vol.37Issue(6):610-613,4.
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
摘要
Abstract
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 x 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 Oh, 4h, 8h and 16h after CBD ligation, the levels of plasma endotoxin, TNF- a, alanine transaminase (ALT) and total bilirubin (TB), CD 14 and nuclear transcription factor-KB (NF-KB) 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- a 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 CD 14 and NF-KB protein expressions. Compared with AOC group, the parameters such as plasma ALT, TB and TNF-α levels, CD14 and NF-KB protein expressions and hepatic histopathological injury decreased significantly in AOC+NAC group (P<0.0l). Conclusions Endotoxin-induced acute liver injury is related to a progressive upregulation of expression of CD 14 and NF-KB in liver tissue during AOSC. NAC may attenuate the endotoxin-induced acute liver injury by down-regulating CD 14, NF-KB 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-κ B/枯否细胞Key words
acetylcysteine/ cholangitis/ lipopolysaccharides/ antigens, CD 14/ NF-kappa B/ Kupffer cells分类
医药卫生引用本文复制引用
薛强,刘作金,杨慷,涂兵,丁雄..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[J].解放军医学杂志,2012,37(6):610-613,4.基金项目
重庆市医学科学技术研究项目(2010-2-156) (2010-2-156)