大黄素致药物性肝损伤大鼠肝组织病理学初步观察*

doi:10.3969/.j.issn.1672-5069.2015.06.011

摘要/Abstract

摘要： 目的研究大黄素致药物性肝损伤（DILI）大鼠肝组织病理学的动态变化情况。方法取Wistar 雄性大鼠100只,随机分成5组,按照每日大黄素摄入量的不同,分为大剂量组（16mg·kg^-1·d^-1）、较大剂量组（8mg·kg^-1·d^-1）、中剂量组（4mg·kg^-1·d^-1）、小剂量组（2mg·kg^-1·d^-1）,给予药物灌胃,和正常组,给予等体积蒸馏水灌胃,每组20只,于实验的4w、8w分别解剖5只大鼠,至12w解剖剩余全部大鼠,观察体质量的变化;同时采用HE染色和VG染色观察肝组织炎症及纤维化情况,并对各组纤维化程度的等级资料采用Radit分析法比较其差异的显著性。结果各组大鼠生长状态无明显差异,各组均无死亡和腹水形成。通过对各组动物体质量的比较,发现在较大剂量组和大剂量组动物体质量下降,在实验12w时,正常组、小剂量组、中剂量组动物体质量分别为（335±10.56） g、（350.4±7.23） g和（338.6±7.54） g,显著重于大剂量组[（300.4±8.91）g,P<0.01],而较大剂量组为（335±10.56）g,与大剂量组差异不显著（P>0.05）;在实验4w和8w时,各种动物肝组织纤维化变化的差异不明显,而在12w时,发现在较大剂量组和大剂量组动物肝组织炎症活动明显,肝组织出现纤维化改变,尤其是在大剂量组更加显著（x²=14.75，P<0.05）。结论随着给动物服用大黄素剂量的增加和时间延长，可能会引起DILI。本实验为药物性肝损伤模型的建立进行了初步研究，需要进一步验证。

关键词: 药物性肝损伤, 大黄素, 病理学, 模型

Abstract: Objective This study is aimed at establishment of emodin-induced drug-induced liver injury in rats. Methods According to dose of emodin daily intake，100 male Wistar rats were randomly divided into five groups，e.g. high-dose group （16mg.kg^-1?d^-1），a larger dose （8 mg?kg^-1?d^-1），the middle dose group （4mg?kg^-1?d^-1），low-dose group （2 mg?kg^-1?d^-1） and the normal control group （fed an equal volume of distilled water），and each group had 20 rats. 5 rats were killed in each group at the end of 4th and 8th week. Other rats were all killed in the end of 12th week. The body weight of rats was measured. With HE and VG staining，the pathology of liver tissues were observed under microscope. The degree of fibrosis in liver tissues were compared by Radit analysis. Results Rats lived good in each group，and there were no deaths in each group or ascites formation;The body weight in high dose group were significantly lighter，and the body weight in normal group，low dose group，and middle dose group at 12th week were（335±10.56） g，（350.4±7.23） g and（338.6±7.54） g，respectively，much heavier than in high dose group[（300.4±8.91）g，P<0.01]；The inflammation activity and degree of hepatic fibrosis in liver tissues were both significantly more obvious in high dose group at 12th week（x²=14.75，P<0.05）. Conclusion The liver injury model in rats could be induced by emodin perfusion，which needs to be explored further in the future.

Key words: Drug-induced liver injury, Emodin, Pathology, Model

张斌，丁慎华，钱雪梅，朱薇珊. 大黄素致药物性肝损伤大鼠肝组织病理学初步观察^*[J]. 实用肝脏病杂志, 2015, 18(6): 607-610.

Zhang Bin， Ding Shenhua， Qian Xuemei， et al.. Emodin-induced drug-induced liver injury in rats[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2015, 18(6): 607-610.

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大黄素致药物性肝损伤大鼠肝组织病理学初步观察^*

Emodin-induced drug-induced liver injury in rats

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