实验性肝硬化大鼠细胞因子il18、tnfα、ifnγ的变化及意义

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1、实验性肝硬化大鼠细胞因子IL18、TNFα、IFNγ的变化及意义作者：党双锁，高宁，程延安，边静，王顺达，孙明珠【摘要】　　目的探讨在四氯化碳(CCl4)复合因素诱导实验性肝硬化大鼠的形成过程中，白介素18(IL18)、肿瘤坏死因子α(TNFα)、γ干扰素(IFNγ)的变化及意义。方法将80只清洁级雄性SD大鼠随机分为正常对照组和造模2周组、4周组、6周组，每组20只。予以CCl4复合因素诱导大鼠肝硬化，并在2、4、6周3个时间点分别处死6只大鼠。采用ELISA法检测大鼠血清IL18、TNF

2、α、IFNγ和肝脏组织匀浆上清液中的IL18含量；HE染色观察肝脏的组织病理学变化。结果①CCl4复合因素诱导的实验性大鼠，组织病理学观察发现，2周时大鼠肝脏组织细胞肿胀变性，6周时有大量纤维增生，部分肝组织有假小叶的形成；②随着造模时间的延长，实验大鼠血清IL18、TNFα、IFNγ水平逐渐升高，造模6周组与正常对照组比较差异有统计学意义(P<0.01)；③造模组肝脏组织匀浆中IL18随肝损害程度的加重而升高，造模6周组与正常对照组比较差异有统计学意义(P<0.01)。结论在CCl

3、4复合因素诱导大鼠肝硬化的形成过程中，IL18、TNFα、IFNγ水平逐渐升高，提示该3种细胞因子与肝硬化的形成及发展有关。【关键词】大鼠；肝硬化；白介素18；肿瘤坏死因子α；γ12干扰素　　ABSTRACT:ObjectiveToinvestigatethechangesofinterleukin18(IL18),tumornecrosisfactorα(TNFα)andinterferonγ(IFNγ)levelsoflivercirrhosisinducedbythecomposit

4、efactorsofcarbontetrachloride(CCl4)inSDratsandtheirsignificance.MethodsTotally80maleSDratsofcleanclasswererandomlydividedintonormalcontrolgroup(20rats)andmodelgroups,thelatterofwhichwerefurtherdividedintothreegroupsaccordingtothelengthofadministrationtime,

5、namely,2weekgroup(2wkgroup),4weekgroup(4wkgroup)and6weekgroup(6wkgroup),with20ratsineach.Sixratswerekilledafter2wk,4wkand6wkadministrationtime,respectively.TheratserumlevelsofIL18,TNFαandIFNγandthehepatichomogenatesupernatantofIL18weredetectedbyELIS

6、A;pathologicalchangesoflivertissueswereobservedbyHEstaining.Results①Pathologicalobservationrevealedthatinthemodelgroupshepaticcellsdegeneratedandswelledatweek2whilelargeamountsoffibrosisandpseudolobulesofsomelivertissuesoccurredatweek6.②TheserumlevelsofIL

7、18,TNFαandIFNγweregraduallyincreasedwiththemodelingtime,andtheyweresignificantly12higherin6weekgroupthaninnormalcontrolgroup(P<0.01).③ThelevelsofhepatichomogenatesupernatantofIL18inthemodelgroupswereelevatedwithliverdamage,andtheyweresignificantlyhi

8、gherin6weekgroupthaninnormalcontrolgroup(P<0.01).ConclusionDuringtheformationoflivercirrhosisinducedbycompositefactorsofCCl4inrats,IL18,TNFαandIFNγlevelsgraduallyincrease,suggestingthatthethreecytokine