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7:12277.[43] Ohno S, Takanashi M, Sudo K, et al. Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol Ther. 2013。nezSales V, Vila V, et al. Circulating endothelial cells and microparticles as prognostic markers in advanced nonsmall cell lung cancer. PLoS One. 2012。107(9):10471057.[29] Li L, Piontek K, Ishida M, et al. Extracellular vesicles carry miR195 to intrahepatic cholangiocarcinoma andimprove survival in a rat . 2016.[30] Helbing T, Olivier C, Bode C, et al. Role of microparticles in endothelial dysfunction and arterial hypertension. World J Cardiol. 2014。9(12):e115316.[20] Cai J, Han Y, Ren HM, et al. Extracellular vesiclemediated transfer of donor genomic DNA to recipient cells is a novel mechanism for genetic influence between cells. J Mol Cell Biol. 2013。763(Pt A):90103.[14] Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013。262:94129420.[6] Cocucci E, Racchetti G, Meldolesi J. Shedding microvesicles: artefacts no more. Trends Cell Biol. 2009。文章版權(quán):文章出版前雜志已與全體作者授權(quán)人簽署了版權(quán)相關(guān)協(xié)議。作者貢獻(xiàn):文章設(shè)計(jì)、實(shí)施、評估為第一作者和通訊作者。此外,細(xì)胞外囊泡能成為理想的藥物載體,可利用電穿孔或脂質(zhì)體轉(zhuǎn)染的方式直接把藥物轉(zhuǎn)入細(xì)胞外囊泡或者將編碼興趣蛋白質(zhì)的基因轉(zhuǎn)入分泌細(xì)胞外囊泡的細(xì)胞以達(dá)到更好的效果[4142]。這類囊泡能通過調(diào)節(jié)免疫炎癥反應(yīng)、調(diào)節(jié)血管內(nèi)皮細(xì)胞及平滑肌細(xì)胞功能、抗纖維化、促血管及細(xì)胞再生、改善受損細(xì)胞的凋亡及增殖等多種機(jī)制對多種疾病發(fā)揮治療作用,且這種作用在組織再生和修復(fù)中尤為突出,能為干細(xì)胞治療非細(xì)胞途徑開辟新路徑[39]。這一作用主要有賴于細(xì)胞外囊泡攜帶的生物信息物質(zhì),尤其是RNA,有文獻(xiàn)報(bào)道,急性冠脈綜合征(ACS)患者血清中,肌特異性miR1和miR133a表達(dá)水平升高,并且這一變化和肌鈣蛋白T(CTnT)水平相關(guān)[7]。細(xì)胞外囊泡也參與體內(nèi)自噬過程,有研究指出,經(jīng)煙霧提取物誘導(dǎo)人氣道上皮細(xì)胞后收集到的HBEC細(xì)胞外囊泡中miR210表達(dá)量上調(diào),后者作圖3 以外泌體為例闡釋細(xì)胞外囊泡與靶細(xì)胞信息傳遞方式圖注:圖A顯示富含母細(xì)胞信息的外泌體從細(xì)胞中釋放出來;B:通過其攜帶的特異性表面分子配體與靶細(xì)胞上相應(yīng)受體位點(diǎn)結(jié)合;C:直接與靶細(xì)胞質(zhì)膜融合,釋放其內(nèi)容物到靶細(xì)胞胞質(zhì)中;D:改變外泌體作用方式時(shí)對靶細(xì)胞影響;E:通過內(nèi)陷以類似胞吞作用的機(jī)制將信息直接傳遞給靶細(xì)胞。 細(xì)胞外囊泡參與細(xì)胞間物質(zhì)、信息傳遞 在生理、病理?xiàng)l件下,細(xì)胞外囊泡將其攜帶生物信息運(yùn)輸?shù)街苓叞屑?xì)胞或經(jīng)血液循環(huán)及體液運(yùn)輸而被遠(yuǎn)處組織細(xì)胞攝取,進(jìn)而對靶細(xì)胞遺傳組進(jìn)行重新編排,使靶細(xì)胞獲得新的功能或失去某功能甚至死亡[28]。Ratajczak等[25]證實(shí)小鼠胚胎干細(xì)胞來源的MVs能把蛋白質(zhì)和mRNA轉(zhuǎn)運(yùn)到造血祖細(xì)胞中,并使其重新編程,這一作用經(jīng)RNase處理微粒后不復(fù)存在,表明有微粒轉(zhuǎn)運(yùn)的mRNA不僅能穩(wěn)定存在于靶細(xì)胞,還能在靶細(xì)胞內(nèi)被翻譯成相應(yīng)蛋白。此外,分離提取細(xì)胞外囊泡的方法還有諸如微孔過濾技術(shù)、微流控技術(shù)、高效液相色譜法以及細(xì)胞外囊泡提取試劑盒。如EMV表達(dá)CD31,PMV表達(dá)CD42b,白細(xì)胞來源的表達(dá)CD45,網(wǎng)織紅細(xì)胞來源的表達(dá)轉(zhuǎn)鐵蛋白受體分子,抗原呈遞細(xì)胞來源的富含MHCⅠ,Ⅱ。細(xì)胞外囊泡形成、釋放的分子機(jī)制不完全清楚,可能與細(xì)胞膜重構(gòu)和細(xì)胞骨架改變有關(guān)。關(guān)于細(xì)胞外囊泡的分類,依據(jù)細(xì)胞來源命名分類是其常見分類方法之一。檢索時(shí)間范圍:2006年7月至2016年8月。隨后的相關(guān)研究多是用術(shù)語膜微粒來描述這類物質(zhì)[3]。 通訊作者:陳建英,主任醫(yī)師,碩士生導(dǎo)師,廣東醫(yī)科大學(xué)附屬醫(yī)院心內(nèi)三區(qū),廣東省湛江市524001 中圖分類號:文獻(xiàn)標(biāo)識碼:A文章編號:20954344(2017)040062106稿件接受:20161126Wang Jin, Master, Graduate School of Guangdong Medical University, Zhanjiang 524001, Guangdong Province, ChinaCorresponding author: Chen Jianying, Chief physician, Master’s supervisor, Third Department of Cardiology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong Province, ChinaAbstractBACKGROUND: Extracellular vesicles (EVs) are a kind of subcellular ponent produced by paracine mechanism including exosomes, microparticles and microvesicles, which have bee hotspots in recent years.OBJECTIVE: To review the research status and progress of EVs, especially in the studies about definition, secreting mechanism, isolation and identification, biological characteristics and functions in diseases as well as in biomedical research. 完美WORD格式編輯 METHODS: The first author retrieved PubMed and CNKI databases for relative articles published from July 2006 to August 2016. The keywords were “extracellular vesicles, exosome, microvesicle, microparticle” in English and Chinese, respectively.RESULTS AND CONCLUSION: A total of 44 eligible literatures are enrolled. Almost all cells can secrete EVs, which contain a variety of metrocytederived bioactive molecules, such as lipids, proteins, mRNAs, microRNA, lncRNA, cicrRNA, and noncoding RNA. These bioactive molecules are encapsulated in EVs or binding with the membrane. EVs are described to be involved in inflammation, immunity, signal transduction, cell survival and apoptosis, angiogenesis, thrombogenesis, and autophagy, wh