目的研究小剂量乙酰半胱氨酸(N-acetylcysteine,NAC)对CCl4所致慢性肝损伤的疗效及其作用机制。方法将大鼠分为正常对照组、模型组、小剂量NAC低、中、高剂量组和阳性对照组。小剂量NAC低、中、高剂量组分别给予45,90,180 mg·kg?1,阳性对照组给予阿拓莫兰54 mg·kg?1,正常对照组和模型组腹腔注射等容积灭菌生理盐水。采用CCl4复制大鼠慢性肝损伤模型,末次给药后24 h麻醉大鼠,腹主动脉取血,检测血清ALT、AST含量以及肝组织中SOD、MDA、GSH和Hyp含量,观察肝脏组织病理学变化,免疫组化检测肝组织Nrf2、HO-1的表达。结果与正常组比较,模型组大鼠血清ALT、AST、MDA和Hyp含量明显升高(P<0.01),SOD、GSH虽有下降趋势,但结果无统计学差异,Nrf2、HO-1蛋白表达均增加,但差异无统计学意义。与模型组比较,小剂量NAC低、中、高剂量组ALT、AST水平明显降低(P<0.01),低、中剂量组SOD、GSH、Hyp含量差异均有显著性(P<0.01或P<0.05),高剂量组GSH、Hyp含量差异均有显著性(P<0.01或P<0.05),各剂量组MDA均有下降趋势,但无统计学意义,低、中、高剂量组Nrf2、HO-1蛋白表达均增加,其中低剂量组差异有统计学意义(P<0.01或P<0.05)。结论小剂量乙酰半胱氨酸对CCl4诱导大鼠慢性肝损伤具有较好的治疗作用,其作用机制可能通过Nrf2/HO-1通路发挥抗氧化应激作用。 Objective To investigate the curative effect and mechanism of low dose N-acetylcysteine ​​(NAC) on chronic liver injury induced by CCl4. Methods The rats were divided into normal control group, model group, low-dose NAC low, medium and high dose groups and positive control group. Low-dose NAC low, medium and high dose groups were given 45,90,180 mg · kg 1, the positive control group given atomoram 54 mg · kg 1, the normal control group and model group intraperitoneal injection of sterile saline volume . CCl4 was used to replicate the model of chronic liver injury in rats. Blood samples were collected 24 h after the last administration and blood samples were taken from abdominal aorta. Serum levels of ALT and AST, and contents of SOD, MDA, GSH and Hyp in liver tissue were measured. Liver histopathology Changes, immunohistochemical detection of liver tissue Nrf2, HO-1 expression. Results Compared with the normal group, the contents of ALT, AST, MDA and Hyp in the model group were significantly increased (P <0.01), while the levels of SOD and GSH in the model group were decreased. However, the results showed no significant difference. The expression of Nrf2 and HO- All increased, but the difference was not statistically significant. Compared with the model group, the levels of ALT and AST in the low, medium and high dose NAC groups were significantly lower (P <0.01), while the SOD, GSH and Hyp contents in the low and middle dose groups were significantly different (P <0.01 or P < 0.05). The levels of GSH and Hyp in high dose group were significantly different (P <0.01 or P <0.05), MDA in all dose groups showed a decreasing trend, but there was no statistical significance. The levels of Nrf2, HO -1 protein expression increased, of which low-dose group was statistically significant (P <0.01 or P <0.05). Conclusion Low-dose acetylcysteine ​​has a good therapeutic effect on CCl4-induced chronic liver injury in rats, and its mechanism may play an anti-oxidative stress role through the Nrf2 / HO-1 pathway.