实用肝脏病杂志
實用肝髒病雜誌
실용간장병잡지
Journal of Practical Hepatology
2015年
6期
607-610
,共4页
张斌%丁慎华%钱雪梅%朱薇珊
張斌%丁慎華%錢雪梅%硃薇珊
장빈%정신화%전설매%주미산
药物性肝损伤%大黄素%病理学%模型
藥物性肝損傷%大黃素%病理學%模型
약물성간손상%대황소%병이학%모형
Drug-induced liver injury%Emodin%Pathology%Model
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。
目的:研究大黃素緻藥物性肝損傷(DILI)大鼠肝組織病理學的動態變化情況。方法取Wistar 雄性大鼠100隻,隨機分成5組,按照每日大黃素攝入量的不同,分為大劑量組(16mg·kg-1·d-1)、較大劑量組(8mg·kg-1· d-1)、中劑量組(4mg·kg-1·d-1)、小劑量組(2mg·kg-1·d-1),給予藥物灌胃,和正常組,給予等體積蒸餾水灌胃,每組20隻,于實驗的4w、8w分彆解剖5隻大鼠,至12w解剖剩餘全部大鼠,觀察體質量的變化;同時採用HE染色和VG染色觀察肝組織炎癥及纖維化情況,併對各組纖維化程度的等級資料採用Radit分析法比較其差異的顯著性。結果各組大鼠生長狀態無明顯差異,各組均無死亡和腹水形成。通過對各組動物體質量的比較,髮現在較大劑量組和大劑量組動物體質量下降,在實驗12w時,正常組、小劑量組、中劑量組動物體質量分彆為(335±10.56) g、(350.4±7.23) g和(338.6±7.54) g,顯著重于大劑量組[(300.4±8.91)g,P<0.01],而較大劑量組為(335±10.56)g,與大劑量組差異不顯著(P>0.05);在實驗4w和8w時,各種動物肝組織纖維化變化的差異不明顯,而在12w時,髮現在較大劑量組和大劑量組動物肝組織炎癥活動明顯,肝組織齣現纖維化改變,尤其是在大劑量組更加顯著(x2=14.75,P<0.05)。結論隨著給動物服用大黃素劑量的增加和時間延長,可能會引起DILI。本實驗為藥物性肝損傷模型的建立進行瞭初步研究,需要進一步驗證。
목적:연구대황소치약물성간손상(DILI)대서간조직병이학적동태변화정황。방법취Wistar 웅성대서100지,수궤분성5조,안조매일대황소섭입량적불동,분위대제량조(16mg·kg-1·d-1)、교대제량조(8mg·kg-1· d-1)、중제량조(4mg·kg-1·d-1)、소제량조(2mg·kg-1·d-1),급여약물관위,화정상조,급여등체적증류수관위,매조20지,우실험적4w、8w분별해부5지대서,지12w해부잉여전부대서,관찰체질량적변화;동시채용HE염색화VG염색관찰간조직염증급섬유화정황,병대각조섬유화정도적등급자료채용Radit분석법비교기차이적현저성。결과각조대서생장상태무명현차이,각조균무사망화복수형성。통과대각조동물체질량적비교,발현재교대제량조화대제량조동물체질량하강,재실험12w시,정상조、소제량조、중제량조동물체질량분별위(335±10.56) g、(350.4±7.23) g화(338.6±7.54) g,현저중우대제량조[(300.4±8.91)g,P<0.01],이교대제량조위(335±10.56)g,여대제량조차이불현저(P>0.05);재실험4w화8w시,각충동물간조직섬유화변화적차이불명현,이재12w시,발현재교대제량조화대제량조동물간조직염증활동명현,간조직출현섬유화개변,우기시재대제량조경가현저(x2=14.75,P<0.05)。결론수착급동물복용대황소제량적증가화시간연장,가능회인기DILI。본실험위약물성간손상모형적건립진행료초보연구,수요진일보험증。
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.