BH3-only成員參與輻射誘導(dǎo)的小鼠肝細(xì)胞凋亡-論文.pdf

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1、第二軍醫(yī)大學(xué)學(xué)報(bào)2014年8月第35卷第8期http：／／www．a(chǎn)jsmmu．eftAcademicJournalofSecondMilitaryMedicalUniversity，Aug．2014，Voi．35，No．8·837·DOI：10．3724／SP．J．1008．2014．00837·論著·BH3-only成員參與輻射誘導(dǎo)的小鼠JK．~[tt胞凋亡陳松，馮旭，鄒贏鋅，欒潔，張術(shù)，周意，儲(chǔ)智勇海軍醫(yī)學(xué)研究所防護(hù)醫(yī)學(xué)研究室，上海200433[摘要]目的研究細(xì)胞凋亡及凋亡相關(guān)基因的表達(dá)在急性肝臟輻射損傷中的作用。方法采用BAIB／c小鼠以c

2、o7射線進(jìn)行全身照射，建立急性肝臟輻射損傷動(dòng)物模型，光鏡和電鏡觀察病變48h。然后采用蛋白質(zhì)印跡分析法檢測(cè)肝組織中Caspase3、Caspase8、Bcl一2、Bcl—xL、Bax、Bad、PUMA和Slug蛋白表達(dá)，并采用原位末端標(biāo)記法(TUNEL染色)檢測(cè)細(xì)胞凋亡。結(jié)果輻照后4h出現(xiàn)肝細(xì)胞變性和凋亡，輻照后12h出現(xiàn)細(xì)胞壞死，輻照后24～48h肝細(xì)胞凋亡達(dá)到峰值并檢測(cè)到Caspase3激活；Bcl一2在輻照后4～24h上調(diào)，于輻照后48h回落；PUMA在輻照后4～48h上調(diào)；Bcl—x、Bad在輻照后6～48h上調(diào)；Bax、Slug僅在輻照后

3、12h上調(diào)。結(jié)論輻射誘導(dǎo)的PUMA、Bad表達(dá)上調(diào)與輻輻照后肝細(xì)胞凋亡增加有關(guān)。[關(guān)鍵詞]肝；輻射損傷；細(xì)胞凋亡；依賴p53上調(diào)的凋亡調(diào)節(jié)子；Bad[中圖分類號(hào)]R818．85[文獻(xiàn)標(biāo)志碼]A[文章編號(hào)]0258—879X(2014)08—0837—05BH3-‘onlymembersareinvolvedinradiation-inducedapoptosisinmouseliverCHENSong，F(xiàn)ENGXu，ZOUYing—xin，LUANJie，ZHANGShu，ZHOUYi，CHUZhi—yongDepartmentofRadiolog

4、icalProtection，NavalMedicalResearchInstitute，Shanghai200433，China[Abstract]ObjectiveTostudytheexpressionofapoptosis—associatedgenesandtheroleofapoptosisinacuteradiation-inducedliverinjury．MethodsAmouseradiationmodel，whichwasirradiatedwith。Coray，wasestablishedinthisstudy，andthe

5、pathologicalchangeswereobservedbylightandelectronmicroscopyfor48hours．Westernblottinganalysiswasusedtomeasuretheexpressionofsomeproteins(Caspase3，Caspase8，Bcl一2，Bcl-xL，Bax，Bad，PUMA，Slug)andTUNELassaywasemployedtoexaminecellapoptosisinmouseliver．ResultsDegenerationandapoptosisw

6、erefoundintheliverat4hafterirradiationandnecrosisoccurredat12hafterirradiation．ThepeakofapoptosiswithactivationofCaspase3inliverwasdetectedduring24—48hafterirradiation．Bcl一2proteinexpressionwasup—regulatedduring4-24hafterirradiation，thenwasdown—regulatedat48h；PUMAproteinwasup—

7、regulatedduring4-48hafterirradiation；Bcl—xLandBadproteinwereup—regulatedduring6-48hafterirradiation；andBaxandSlugproteinwereup—regulatedonlyat12hafterirradiation．ConclusionUp—regulationofBH3一onlymembers(PUMAandBad)afterirradiationmaybeassociatedwiththeincreaseofapoptoticcellsi

8、nthe1iver．[-Keywords]liver；radiationinjuries；apoptom‘s；p53up—