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1、軍事醫(yī)學(xué)2014年3月第38卷第3期MilMedSci,Vol38,No3,Mar,2014181急性肝損傷過程中肝內(nèi)不同來源巨噬細(xì)胞的作用研究陳芳艷,郝運(yùn)偉,林巍然,范旭,姜穎,賀福初[摘要]目的急性肝損傷過程中,肝臟內(nèi)存在來源不同的兩類巨噬細(xì)胞即肝臟固有巨噬細(xì)胞和單核細(xì)胞源性巨噬細(xì)胞。該研究明確這兩類巨噬細(xì)胞在急性肝損傷過程中的作用。方法采用腹腔注射四氯化碳(CC1)構(gòu)建急性肝損傷小鼠模型,通過流式細(xì)胞術(shù)分析注射CC14后24、48、72h時(shí)小鼠肝內(nèi)巨噬細(xì)胞表面抗原(CD45,F(xiàn)4/80,Iv6c和CD11b)的表達(dá)情況,分選出肝臟固有巨噬細(xì)胞(cD45F4/80)和單核細(xì)胞源
2、性巨噬細(xì)胞(CD45F4/80),并應(yīng)用qRT—PCR檢測(cè)兩群巨噬細(xì)胞中細(xì)胞因子的表達(dá)情況。結(jié)果與正常對(duì)照相比,注射CC1后24、48、72h時(shí)小鼠肝內(nèi)總F4/80細(xì)胞數(shù)顯著增加,尤其是72h時(shí);24hCD45F4/80細(xì)胞數(shù)顯著增加。急性肝損傷過程中,與if_常對(duì)照相比,F(xiàn)4/80巨噬細(xì)胞和F4/80巨噬細(xì)胞中MCP一1、TNF—ot、TGF—pl、基質(zhì)金屬蛋白酶(MMP)一12和MMP一13mRNA水平均顯著升高,IL.1213和IL-6mRNA水平只在F4/80巨噬細(xì)胞中顯著升高,MMP-9mRNA水平只在F4/80巨噬細(xì)胞中顯著升高。與F4/80巨噬細(xì)胞相比,F(xiàn)4/80巨噬
3、細(xì)胞中MCP一1和MMP一12mRNA水平顯著升高,TNF一mRNA水平顯著降低。結(jié)論急性肝損傷時(shí),肝內(nèi)固有巨噬細(xì)胞和單核細(xì)胞源性巨噬細(xì)胞均表達(dá)炎性細(xì)胞因子,促進(jìn)炎癥反應(yīng),導(dǎo)致肝損傷;肝內(nèi)固有巨噬細(xì)胞募集炎性單核細(xì)胞的能力和表達(dá)炎性細(xì)胞因子(IL一1213,IL一6)、MMP一12的能力強(qiáng)于單核細(xì)胞源性巨噬細(xì)胞;單核細(xì)胞源性巨噬細(xì)胞表達(dá)炎性細(xì)胞因子(TNF一0【)和MMP-9的能力強(qiáng)于固有巨噬細(xì)胞。[關(guān)鍵詞]急性肝損傷;肝臟固有巨噬細(xì)胞;單核細(xì)胞來源的巨噬細(xì)胞[中圖分類號(hào)]Q28;Q291[文獻(xiàn)標(biāo)志碼]A[文章編號(hào)]1674-9960(2014)03-0181-08DOI:10.7
4、644/j.issn.1674—9960.2014.03.006RoleofhepaticmacrophagesinacuteliverinjuryCHENFang—yan,HAOYun—wei,LINWei—ran,F(xiàn)ANXu,JIANGYing,HEFu—chu(StateKeyLaboratoryofProteomics,BeijingProteomeResearchCenter,BeijingInstituteofRadiationMedicine,Beijing102206,China)Correspondingauthor.E-mail:hefc@bmi.a(chǎn)c.a(chǎn)n[A
5、bstract]ObjectiveToelaboratetheroleofhepaticinherentmacrophagesandmonocyte-derivedmacrophagesinacuteliverinjury.MethodsAmodelofacuteliverinjuryinmicewasinducedviaintraperitoneallyinjectionofCC1d.Af_terCCI4injection,analysisoftheexpressionofCD45,F(xiàn)4/80,Ly6CandCD11bonthehepaticmacrophagesurfacewa
6、sperformedbyflowcytometryat24,48and72hbeforethehepaticinherentmacrophages(CD45F4/80“)andmonocyte—de—rivedmacrophages(CIM5F4/80)weresortedatthesametime.Therelativeexpressionofcytokinesinthetwopopula—tionsofmacrophageswasdetectedbyqRT—PCR.ResultsComparedwithcontrol,thenumberoftotalF4/80cellsinth
7、eliverwasmarkedlyincreasedafterCC14injection,especiallyat72h.ThenumberofCIM5F4/80”cellsincreasedsignifi—cant]Ya"fterCC14injection24h.ThemRNAlevelsofMCP一1,TNF·0I,TGF—p1,matrixmetalloproteinase(MMP)一12andMMP一13wereelevatedsignificantlybot