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1、中國細(xì)胞生物學(xué)學(xué)報(bào)ChineseJournalofCellBiology2014,36(6):805—809DOI:10.11844/cjcb.2014.06.0435對乙酰氨基酚誘導(dǎo)的小鼠藥物性肝損傷的模型研究李大偉陸天飛華相偉張健健王維剛崔小蘭戴繪娟張明夏強(qiáng)(上海交通大學(xué)醫(yī)學(xué)院附屬仁濟(jì)醫(yī)院肝臟外科,上海200127;。上海南方模式生物研究中心,上海201203)摘要改良對乙酰氨基酚(acetaminophen,APAP)單獨(dú)誘導(dǎo)小鼠急性肝損傷的模型和致死模型。隨機(jī)將小鼠分為4組:空白對照組、APAP3h組、A
2、隊(duì)P6h組和APAP12h組,每組5Z。饑餓15h后用對乙酰氨基酚誘發(fā)小鼠肝損傷。測定各組血清ALT、AsT及膽紅素含量,HE染色觀察各組肝組織損傷情況。觀察生存率時(shí),小鼠隨機(jī)分為對照組、禁食+APAP(500mg/kg)組、禁食+APAP(300mg/kg)~和不禁食+APAP(500mg/kg)$~_,四組同時(shí)給藥,然后記錄各組小鼠的生存情況,繪制四組小鼠的生存曲線。小鼠注射APAP后,隨時(shí)間的延長,ALT、AST水平逐漸升高,均明顯高于空白對照組<0.05)。小鼠肝臟HE染色可見,APAP中毒組小鼠肝細(xì)胞壞
3、死及炎性細(xì)胞浸潤。禁食+APAP(500mg/kg)8~小鼠自16h開始出現(xiàn)死亡,72h時(shí)全部死亡,死亡率明顯高于不禁食組和禁食+APAP(300mg/kg)~.小鼠。該研究對APAP~I起的C57/BL6小鼠藥物性肝損傷模型進(jìn)行改良,使其更加穩(wěn)定和便于研究,為進(jìn)一步探究APAP誘導(dǎo)肝毒性的機(jī)制及防治措施奠定了基礎(chǔ)。關(guān)鍵詞急性肝損傷:對乙酰氨基酚:動(dòng)物模型TheModelofAcuteLiverInjuryInducedbyAcetaminopheninMiceLiDawei,LuTianfei,HuaXiang
4、wei,ZhangJianjian,WangWeigang,CuiXiaolan,DaiHuijuan,ZhangMing,XiaQiang(DepartmentofLiverSurgery,RenjiHospital,SchoolofMedicine,ShanghaiJiaoTongUniversity,Shanghai200127,China;。ShanghaiResearchCenterofModelOrganisms,Shanghai201203,China)AbstractTheaimofthestud
5、ywastoimprovetheacuteliverinjurymodelandletha1modelofmicein-ducedbyacetaminophen(APAP)injection.20miceweredividedinto4groupsrandomly:normalcontrol,APAP3hgroup,APAP6hgroup,andAPAP12hgroup.Micewerefastedfor15hoursbeforeAPAPinjectiontoinduceliverinjury.Weassayed
6、serumalanineaminotransferase(ALT),aspartateaminotransferase(AST)andexam—inedliverpathologicchangesafterinjectionbyHEstaining.20miceweredividedintofourgroups:con—trolgroup,fast+APAP(500mg/kg)group,fast+APAP(300mg/kg)groupandnon—fast+APAP(500mg/kg)group.Thefour
7、groupswereadministratedatthesametime.WeobservedthesurvivalstatusofmicebeforeandafterAfIAPadministrationandmadesurvivalcurve.SerumAIandASTlevelsincreasedbytimeafterAPAPadminis—trationandweresignificantlyhigherthanthatincontrolgroupP<0.05).LiverspecimensofAPlAP
8、micedisplayedcharacteristiccentrilobularnecrosisandinflammatoryinfiltration.Allmiceoffast+APAP(500mg/kg)groupdiedwithin16to72hours,andthemortalitywassignificantlyhigherthanthoseoftheother