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目的:研究抗结核药(HRZ)与阿托伐他汀联用致肝损伤的特征及其机制。方法:随机把入选动物分为4组(空白对照组、HRZ组、阿托伐他汀组和阿托伐他汀+HRZ组),分别给予相应药物灌胃给药后于第10天、第35天及第55天检测并观察其肝功能指标、HE染色、CYP3A4和CYP2E1免疫组化染色以及CYP2E1原位杂交表达情况。结果:除空白对照组外,用药组均有肝损伤的发生,并与投药时间具有相关性,但阿托伐他汀+HRZ组(联用组)较单一用药组肝损伤程度更为严重。结论:这两类药物联合治疗于同一个体时,应慎重权衡药物性肝损伤的因素,在联合应用时应检测肝功能相关指标及肝活检的时间位点,推测肝功能损伤的加重可能与这两类药物联用后诱导CYP3A4和CYP2E1的表达有关。
Objective: To study the characteristics and mechanism of hepatic injury induced by combination of antituberculosis drugs (HRZ) and atorvastatin. Methods: The animals were randomly divided into 4 groups (blank control group, HRZ group, atorvastatin group and atorvastatin + HRZ group), and were given the corresponding drugs after gavage on day 10, day 35 And on the 55th day, the liver function index, HE staining, CYP3A4 and CYP2E1 immunohistochemical staining and CYP2E1 in situ hybridization were detected and observed. Results: Except for the blank control group, the liver injury occurred in both groups and was related to the administration time. However, atorvastatin + HRZ group (combination group) had a more severe liver injury than the single group. Conclusion: The combination of these two drugs in the same individual should be carefully weighed against the factors of drug-induced liver injury, when used in combination should be detected liver function-related indicators and time points of liver biopsy, presumably aggravating liver injury may be related to this Two types of drugs combined with the induction of CYP3A4 and CYP2E1 expression.