N-乙酰半胱氨酸对小鼠免疫性肝损伤的影响

目的研究N-乙酰半胱氨酸(NAC)对卡介苗(BCG)与细菌脂多糖(LPS)引起小鼠免疫性肝损伤的影响。方法建立BCG/LPS引起的小鼠免疫性肝损伤模型。采用两种处理方式给予NAC:方式A,于LPS处理前4h和15min分别经腹腔注射给予NAC(预处理);方式B,于LPS处理后0h和4h分别经腹腔注射NAC(后处理)。LPS处理后8h剖杀动物,取血和肝脏,并检测血清丙氨酸氨基转移酶(ALT)活性与一氧化氮(NO)水平、肝脏组织谷胱甘肽(GSH)与丙二醛(MDA)含量以及肿瘤坏死因子α(TNF-α) mRNA表达水平。结果与模型组比较,NAC预处理组小鼠血清ALT活性下降,肝脏TNF-α mRNA表达明显减少,而体内NO生成和肝脏脂质过氧化水平无改变;NAC后处理组与模型组相比,小鼠死亡率升高,血清NO生成增加,肝脏GSH含量进一步下降,而小鼠血清ALT活性未见明显改变。结论NAC对小鼠免疫性肝损伤有双重效应,NAC预处理对抗BCG/LPS引起的小鼠免疫性肝脏损伤,NAC后处理加重BCG/LPS引起的氧化应激并升高动物死亡率。

Effects of N-acetylcysteine on immunological liver injury in mice

Aim To study effects of N-Acetylcysteine on Lipopolysaccharide-induced immunological liver injury in mice. Methods A model of immunological liver injury was induced by injection of LPS in mice primed with BCG. NAC was administered in two different modes. In mode A, mice were pretreated with two doses of NAC before LPS, one (150 mg·kg-1, ip) at 4 h before LPS and the other (150 mg·kg-1, ip) at 15 min before LPS. In mode B, mice were administered with two doses of NAC after LPS, one (150 mg·kg-1, ip) injected immediately after LPS and the other (150 mg·kg-1, ip.) injected 4 h after LPS. Some mice were sacrificed at 1.5 h after LPS and livers were dissected for total RNA extraction. Hepatic TNF-α mRNA level was determined by using RT-PCR. The remaining mice were sacrificed at 8 h after LPS. Blood serum was collected for measurement of alanine aminotransferase (ALT) and nitrate plus nitrite. Livers were dissected for measurements of GSH and lipid peroxidation. Results Pretreatment with NAC significantly alleviated LPS-induced increase in ALT activity, attenuated LPS-induced hepatic GSH depletion and TNF-α mRNA expression in mice primed with BCG. However, NAC had no effects on LPS-induced NO production and hepatic lipid peroxidation. By contrastwith pretreatment, posttreatment with NAC had littleeffects on LPS-induced immunological liver injury and in fact aggravated LPS-induced NO production and hepatic GSH depletion and increased LPS-induced mortality in mice primed with BCG. Conclusion NAC has a dual effect on LPS-induced immunological liver injury. Pretreatment with NAC protects against LPS-induced immunological liver injury via counteracting LPS-induced oxidative stress and TNF-α mRNA expression in mouse liver. However, when administered after LPS, NAC behaves as a prooxidant and aggravates LPS-induced mortality in mice primed with BCG.