阿托伐他汀联合HRZ致肝损伤生化特点
Biochemical Characteristics of Liver Injury Induced by Atorvastatin Combined HRZ
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摘要: 目的 分析阿托伐他汀联合HRZ (异烟肼+利福平+吡嗪酰胺) 致药物性肝损伤的生化特点, 为临床合理用药提供相关理论依据.方法 SPF级8周龄SD大鼠80只, 雌雄各半, 随机分为4组:空白对照组、阿托伐他汀组、HRZ组、阿托伐他汀+HRZ组, 按人-鼠间药物剂量换算, 分别予相应药物灌胃给药, 于10 d、20 d、40 d通过股动脉取血并分别检测各组大鼠的肝功能指标:总胆红素 (TBIL) 、直接胆红素 (DBIL) 、间接胆红素 (IBIL) 、谷草转氨酶 (AST) 、谷丙转氨酶 (ALT) 、碱性磷酸酶 (ALP) .结果 在给药10 d、20 d、40 d时用药组TBIL、DBIL、IBIL较空白组升高 (P<0.05) ;在给药10 d时, 联合用药组AST较空白组升高 (P<0.05) ;在用药过程中各组间ALT差异无统计学意义 (P>0.05) ;分别在给药20 d和40 d时, 阿托伐他汀组与HRZ组ALP 2组间比较均具差异有统计学意义, 以HRZ组损伤较重 (P<0.05) , 联合用药组较HRZ组升高 (P<0.05) .结论 3组实验组大鼠造成肝损伤均为轻中度损伤;其致肝损伤主要为胆汁淤积型;其中以阿托伐他汀联合HRZ致肝损伤最重且随用药时间延长而加重.Abstract: Objective To provide theoretical basis for the rational use of drugs in clinic, the biochemical characteristics of liver injury induced by Atorvastatin Combined with HRZ (Isoniazid Rifampicin and Pyrazinamide) were analyzed in animal model. Me thods Eighty 8 week old SPF SD rats with half males and females were divided into four groups: control group, atorvastatin group, HRZ group, atorvastatin+HRZ group. According to the human mouse drug dose conversion, mice were given corresponding drugs by gavage.Hepatic function index of rats (the Total bilirubin, Direct bilirubin, Indirect bilirubin, Aspartate aminotransferase, Alanine aminotransferase, Alkaline phosphatase) were detected by blood from the femoral artery and hepatic function index of rats in each group on 10 d, 20 d, 40 d.Re s ults There were significant difference in the anmmistrated group on 10, 20, 40 days with higher TBIL, DBIL, IBIL than that in control group; in the admimistrated group on Day 10, combined treatment group was higher than that in cotrol group and there were significant differences in ALT;in the process of treatmen, there was statistical difference; ALP was administered for 20 days and the 40 day, atorvastatin there was HRZ group was statistically different in groupHRZ, severe injury, combination group compared with HRZ group had statistically significant difference. Conclus ions The liver injury in the three experimental groups is mild and moderate, and the liver damage is mainly cholestasis type. The most severe hepatic injury caused by Atorvastatin Combined with HRZ is aggravated by the prolonged use of drugs.
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Key words:
- Drug-induced liver injury /
- Biochemical characteristics /
- Damage mechanism
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