N-乙酰半胱氨酸对大鼠胆道梗阻肝功能损伤的保护作用及机制研究

摘要

Objective To investigate the mechanisms of N-acetylcysteine protection against liver injury caused by biliary tract obstruction in rats. Methods Seventy-two Wistar rats were divided randomly into the following three groups: (1) Rats received choledochus ligationon and N-acetylcysteine by intraperitoneal injection (DBL+NAC); (2) Rats received choledochus ligationon only; (3) sham operation. Six rats were killed each time after 1 d, 3 d, 5 d and7 d and their liver function was tested by TBA-40FR Automatic Chemistry Analyzer. In addition, NO production was detected by Griess Reagent System. Results When the period of biliary duct obstruction is extended, serum AST,ALT,TBIL, DBIL, NO and TNF-α increase but the increase in serum ALT, AST, NO and TNF-α(P＜0. 05) is more prominent in group DBL than group DBL+NAC at any given time. Conclusions N-acetylcysteine can effectively protect against liver injury in rats with obstructive jaundice, and this may be achieved through down-regulation of TNF-α and NO in hepatocytes.%目的 探讨N-乙酰半胱氨酸(N-acetylcysteine，NAC)对大鼠胆道梗阻所致肝功能损伤的保护作用及其机制。方法Wistar大鼠72只随机均分成3组：(1)胆道结扎+NAC组(DBL+NAC，n=24)：开腹结扎并切断胆总管，建模成功后经腹腔注射NAC（150 mg·kg-1·d-1）连续注射7 d；(2)胆道结扎组（DBL组，n=24）；(3)假手术组(SO组，n=24)：仅行开腹游离胆总管不予结扎和切断。建模成功后1、3、5、7d每组分别活杀6只大鼠，取静脉血及肝组织，检测肝功能、血浆肿瘤坏死因子α(TNF-α)在各时相点的变化并采用Griess法检测一氧化氮(NO)产生情况。结果 在DBL组、DBL+ NAC组谷-草转氨酶(AST)、血清谷丙转氨酶(ALT)、总胆红素(TBIL)、直接胆红素(DBIL)均随胆道梗阻时间延长而升高，但DBL组AST、ALT在各时间点均较DBL+NAC组明显升高(P＜0.05)，而TBIL、DBIL在这两组间无明显差异(P＞0.05)。DBL组和DBL+ NAC组TNF-α、NO浓度变化也随梗阻时间延长而升高，但DBL组较DBL+ NAC组TNF-α、NO浓度升高更明显(P＜0.05)。结论N-乙酰半胱氨酸能有效改善胆道梗阻所致肝损害，并有可能是通过下调肝组织中TNF-α、NO的表达这一途径实现的。