小剂量乙酰半胱氨酸治疗慢性肝损伤作用及其机制

Therapeutic Efficacy and Mechanisms of Low Dose Broncholysin on CCl4 Induced Chronic Hepatic Injury In Rats

关键词:  小剂量乙酰半胱氨酸  CCl₄  慢性肝损伤  核因子NF-E2相关因子/血红素氧化酶通路  机制

Key words:  low dose N-acetylcysteine  CCl₄  chronic hepatic injury  nuclear factor erythroid-2 related factor 2/hemeoxygenase-1(Nrf2/HO-1)  mechanism

摘要:

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。

Abstract:

OBJECTIVE To investigate therapeutic effects and mechanisms of low dose broncholysin on CCl₄ induced chronic hepatic injury in rats. METHODS Rats were divided into control group, model group, low dose NAC low, middle and high dose group, and positive control group. Rats in low dose NAC low, middle and high dose group were given NAC 45, 90, 180 mg·kg^-1 respectively. Rats in positive control group were given atomolan 54 mg·kg^-1. Rats in control group and model group were given sterilized normal saline. A chronic hepatic injury model was induced via intraperitoneal injection of CCl₄. 24 h after the last administration, the levels of ALT, AST in serum and SOD, MDA, GSH and Hyp in hepatic tissue content were detected. Liver histopathological changes were observed. Immunohistochemistry was used to detect the expression of Nrf2 and HO-1 in hepatic tissue. RESULTS Compared with rats in the model group, the levels of ALT, AST, MDA and Hyp raised(P<0.01), levels of GSH and SOD decreased, protein express of Nrf2 and HO-1 raised, but there were no statistically significant. Compared with rats in the control group, ALT, AST in serum of three NAC groups all decreased(P<0.01), SOD, GSH and Hyp in low and medium dose groups, GSH, Hyp in high dose group had statistically significant(P<0.01 or P<0.05), MDA in the three NAC groups decreased, but there were no significant. Nrf2 and HO-1 were increased in the three NAC groups, and the low dose groups there was statistically significant. CONCLUSION Low dose broncholysin play an important role in preventing chronic hepatic injury of the rats. Low dose broncholysin treatment may help to against oxidative stress by regulating the expression of Nrf2 and HO-1.