吡咯里西啶生物碱相关肝损害血液系统变化的初步研究  

Preliminary study of the changes in blood system in pyrrolizidine alkaloid-related liver damage

作　　者：陈昀 蒋虹玥 李冬平 陈思诺 王吉耀[1,2] 高虹[1,2] Chen Yun;Jiang Hongyue;Li Dongping;Chen Sinuo;Wang Jiyao;Gao Hong(Department of Gastroenterology and Hepatology,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Evidence-based Medicine Center of Fudan University,Shanghai 200032,China)

机构地区：[1]复旦大学附属中山医院,上海200032 [2]复旦大学循证医学中心,上海200032

出　　处：《中华肝脏病杂志》2021年第6期533-538,共6页Chinese Journal of Hepatology

基　　金：复旦大学附属中山医院优秀骨干培养计划 (2019ZSGG12)。

摘　　要：目的初步探索吡咯里西啶生物碱(PAs)相关性肝损害的血液系统变化。方法回顾性分析复旦大学附属中山医院2012-2019年间收治的77例药物性肝损害患者的一般情况、肝功能血生化检测、血常规、凝血功能指标等,并根据服药史将患者分为PA组、其他中药组和西药组。同时建立野百合碱诱导肝损害小鼠模型,观察小鼠肝功能、肝组织HE染色和血常规各项指标的改变。结果服用PA患者24例,服用其他中药患者24例,服用西药患者29例。PA组患者丙氨酸转氨酶较其余两组患者低(P<0.05),总胆红素和直接胆红素均显著低于其他中药组患者(P<0.05)。PA组患者外周血小板计数为(84.11±26.91)×10^(9)/L,显著低于正常下限,且与其他中药组和西药组患者血小板计数存在统计学差异(P<0.01)。PA组患者血小板压积、平均血小板体积和血小板分度与其他两组存在统计学差异(P<0.05)。PA组患者D-二聚体为(2.62±1.93)mg/L,高于正常值上限,且显著高于其他两组患者的D-二聚体水平(P<0.01);同时PA组患者凝血酶原时间较其他两组延长(P<0.01)。在野百合碱诱导肝损害小鼠模型中可以观察到小鼠在出现丙氨酸转氨酶、天冬氨酸转氨酶升高后,出现血小板明显下降(P<0.01)。结论PA相关性肝损害外周血小板降低,此类患者外周血小板计数较其他类型药物性肝损害患者低。PA相关性肝损害患者D-二聚体明显升高,提示潜在血栓形成风险。Objective To preliminary explore the changes in blood system in pyrrolizidine alkaloids(PAs)-related liver damage.Methods General situation,liver function,biochemical blood test,routine blood test,coagulation function markers,etc.,of 77 cases with drug-induced liver damage admitted to the Zhongshan Hospital Affiliated to Fudan University from 2012 to 2019 were retrospectively analyzed.Patients’were divided into PA group,other traditional Chinese medicine group and Western medicine group according to their medication history.Simultaneously,the changes in liver function were observed in the established mice model of monocrotaline-induced liver damage.Liver tissues HE staining and blood routine indexes were observed.Results 24 cases received PA,24 cases received other traditional Chinese medicine,and 29 cases received western medicine.Alanine aminotransferase was lower in PA group than the other two groups(P<0.05),and the total bilirubin and direct bilirubin were significantly lower than the other traditional Chinese medicine group(P<0.05).The peripheral platelet count of the PA group was(84.11±26.91)×10^(9)/L,which was significantly lower than the lower limit of normal,and had statistically significant difference with other traditional Chinese medicine and western medicine group(P<0.01).Thrombocytocrit,mean platelet volume and platelet indices of PA group were statistically different from the other two groups(P<0.05).The D-dimer level in patients with PA group was(2.62±1.93)mg/L,which was higher than the upper limit of normal,and significantly higher than the D-dimer level of the other two groups of patients(P<0.01).Meanwhile,prothrombin time was longer in PA group than that of the other two groups(P<0.01),and platelets count were decreased significantly in the mouse model of monocrotaline-induced liver damage after alanine aminotransferase and aspartate aminotransferase elevation(P<0.01).Conclusion PA-related liver damage has lower peripheral platelet counts,and the peripheral platelet counts of these patient

关 键 词：药物性肝损害 血液系统 血小板 D-二聚体 吡咯里西啶生物碱 

分 类 号：R969.3[医药卫生—药理学]