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
-
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.
-
Key words:
- Drug-induced liver injury /
- Biochemical characteristics /
- Damage mechanism
-
[1]姚飞, 汪燕燕.综合分析药物性肝损伤9355例[J].安徽医药, 2011, 15 (10) :1313. [2]邓利娟, 梁成罡, 范慧红.几种多组分生化药注射剂降压物质的探讨[J].中国药事, 2010, 24 (6) :546-549. [3]邱玲.药物性肝损伤临床特点及其预后影响因素的研究[D].长春:吉林大学 (硕士论文) , 2012. [4]胡琴, 刘维, 邵宏.药物性肝损伤的药物治疗研究进展[R].中国临床药理学与治疗学, 2016, 21 (2) :232. [5]祖可佳, 张立洁, 常静, 孟欣.药物性肝损伤临床病理分析[J].航空航天医药, 2009, 20 (10) :7. [6]许维国.药物性肝损伤临床特点分析[D].天津:天津医科大学 (硕士论文) , 2014. [7]秦川.常见人类疾病动物模型的制备方法.北京:北京医科大学出版社, 2007:43-50. [8]宋乐, 江晓静.139例药物性肝损伤临床分析[J].中国药学导刊, 2013, 15 (8) :1356. [9]王松原.基于药物相互作用所致肝损害的临床案例分析及机制探讨[D].兰州:兰州大学 (硕士论文) , 2014, 5:4. [10]陈善萍, 董碧蓉.临床医生应关注多药应用和药物相互作用[J].现代临床医学, 2013, 39 (6) :445-459. [11]位松华.ALT、AST、ALP、γ-GT组合实验室检验结果分析在各类肝胆疾病诊断中的临床价值[J].检验医学与临床, 2016, 13 (6) :849. [12]赵东明.阿托伐他汀联合辅酶Q10抑制心室重构的作用机制[D].长春:吉林大学 (硕士论文) , 2013. [13]曾含清, 张琼, 彭文兴.阿托伐他汀致肝损伤的机制[J].药物不良反应杂志, 2012, 12 (4) :232. [14]张云, 郭宏丽, 张陆勇, 江振洲.吡嗪酰胺肝脏毒性的研究进展[J].2014, 37 (6) :559. [15]贾忠, 吴晶, 马建军等.一线抗结核药物肝损害的研究现状[J].中国防痨杂志, 2013, 35 (6) :469. [16]赵红, 程澄, 谢雯.抗结核药物致肝损伤的发病机制[J].中国肝脏病杂志, 2015, 7 (4) :11-12. [17]何雪.PDTC对异烟肼、利福平合用诱导的大鼠肝损伤的影响及其可能机制的研究[D].合肥:安徽医科大学 (硕士论文) , 2015. [18]周利婷.基于转运体初探利福平和或异烟肼致大鼠肝损伤的机制及甘草酸单铵对其的保肝作用[D].兰州:兰州大学 (硕士论文) , 2014. [19]周应初, 刘斌.抗结核药致肝损害的研究进展[J].国际病理科学与临床杂志, 2011, 31 (4) :362. [20]杨波, 吴元凯.ALT、AST、TBil及PT变化趋势与慢加急性乙型肝炎肝衰竭预后的关系[J].临床肝胆病杂志, 2012, 28 (3) :208 -
点击查看大图
计量
- 文章访问数: 1488
- HTML全文浏览量: 536
- PDF下载量: 60
- 被引次数: 0
下载:
