外泌体作为中药载体治疗心血管疾病研究进展
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摘要
外泌体是一种具有双分子磷脂结构,直径为30～100μm的囊状小泡,表面含有DNA、RNA、蛋白质、脂质等多种生物活性物质,可以远距离传递生物信息,因此被称为"天然药物载体",在心血管领域具有重要价值。传统中医药在治疗心血管疾病方面虽具有完整的理论体系和良好的临床疗效,但因其有效成分溶解度低、生物利用度不高,治疗过程长,见效慢等缺点,限制了药物充分利用。而利用外泌体这种新型药物载体,能使药物的有效成分直接递送至靶细胞,更好、更快的发挥药物的作用。本文就外泌体的生物学特征、功能特点及其作为中药载体的研究进展进行综述。
Exosomes are vesicular vesicles with a diameter of 30-100 μm and have bimolecular phospholipid structure. The surface contains DNA, RNA, protein, lipids and other biological active substances, which can transmit biological information from a distance. Therefore, it is called "natural drug carrier" and has important value in the cardiovascular field. Traditional Chinese medicine has a complete theoretical system and good clinical efficacy in the treatment of cardiovascular diseases, but due to its low solubility of active ingredients, low bioavailability, long treatment process, and slow effectiveness, it limits the use of drugs. The use of exosome, a novel drug carrier, enables the drug's active ingredients to be delivered directly to the target cells, allowing better and faster drug action. This article describes the biological characteristics, functional characteristics of exosomes and their research progress as carriers of Chinese medicine.
Exosomes are vesicular vesicles with a diameter of 30-100 μm and have bimolecular phospholipid structure. The surface contains DNA, RNA, protein, lipids and other biological active substances, which can transmit biological information from a distance. Therefore, it is called "natural drug carrier" and has important value in the cardiovascular field. Traditional Chinese medicine has a complete theoretical system and good clinical efficacy in the treatment of cardiovascular diseases, but due to its low solubility of active ingredients, low bioavailability, long treatment process, and slow effectiveness, it limits the use of drugs. The use of exosome, a novel drug carrier, enables the drug's active ingredients to be delivered directly to the target cells, allowing better and faster drug action. This article describes the biological characteristics, functional characteristics of exosomes and their research progress as carriers of Chinese medicine.
引文
[1]王晓景,张军平,李明.精准医学理念在中医药防治心血管病中的应用[J].中华中医药杂志,2017,32(3):972-975.
[2]袁鹏,郭晓辰,张军平,等.外泌体作为中药载体的研究进展[J].药学学报,2017,52(11):1667-1672.
[3]JOHNSTONE R M.Maturation of reticulocytes:formation of exosomes as a mechanism for shedding membrane proteins[J].Biochem Cell Bio,1992,70(3-4):179-90.
[4]MALIK Z A,KOTT K S,POE A J,et al.Cardiac myocyte exosomes:stability,HSP60,and proteomics[J].Am J Phy Heart Cir Phys,2013,304(7):954-65.
[5]JENJAROENPUN P,KREMENSKA Y,NAIR V M,et al.Characterization of RNA in exosomes secreted by human breast cancer cell lines using next-generation sequencing[J].Peer J,2013(1):e201.
[6]BATRAKOVA E V,KIM M S.Using exosomes,naturallyequipped nanocarriers,for drug delivery[J].J Control Release,2015(219):396-405.
[7]WIKLANDER O P,NORDIN J Z,O’LOUGHLIN A,et al.Extracellular vesicle in vivo biodistribution is determined by cell source,route of administration and targeting[J].JExtracell Vesicles,2015(20):1-13.
[8]张亚飞,王瑜,魏良君.外泌体在精准医疗中的应用潜力[J].生物产业技术,2018(2):65-75.
[9]TAVERNA S,AMODEO V,SAIEVA L,et al.Exosomal shuttling of miR-126 in endothelial cells modulates adhesive and migratory abilities of chronic myelogenous leukemia cells[J].Mol Cancer,2014(13):169.
[10]CAMUSSI G,DEREGIBUS M C,BRUNO S,et al.Exosomes/microvesicles as amechanism of cell-to-cell communication[J].Kidney International,2010,78(9):838-848.
[11]曾维凯,陈建英.外泌体治疗心肌梗死及其相关信号通路的研究进展[J].广东医学,2016,37(21):3295-3297.
[12]LEE M J,PARK D H,KANG J H.Exosomes as the source of biomarkers of metabolic diseases[J].Ann Pediatr Endocrinol Metab,2016,21(3):119-125.
[13]HOEFER I E,STEFFENS S,ALA-KORPELA M,et al.Novel methodologies for biomarker discovery in atherosclerosis[J].Eur Heart J,2015,36(39):2635-2642.
[14]KUWABARA Y,ONO K,HORIE T,et al.Increased microRNA-1 and microRNA-133a levels in serum of patients with cardiovascular disease indicate myocardial damage[J].Circ Cardiovasc Genet,2011,4(4):446-454.
[15]HORSTMAN L L,JY W,JIMENEZ J J,et al.Endothelial microparticles as markers of endothelial dysfunction[J].Front Biosci,2004(9):1118-1135.
[16]SADALLAH S,EKEN C,MARTIN P J,et al.Microparticles(ectosomes)shed by stored human platelets downregulate macrophages and modify the development of dendritic cells[J].Journal of Immunology,2011,186(11):6543-6552.
[17]MA J,ZHAO Y,SUN L,et al.Exosomes derived from Aktmodifed human umbilical cord mesenchymal stem cells improve cardiac regeneration and promote angiogenesis via activating platelet-derived growth factor D[J].Stem CellsTransl Med,2017,6(1):51-59.
[18]ZHU L P,ZHOU J P,ZHANG J X,et al.MiR-15b-5p regulates collateral artery formation by targeting AKT3(protein kinase B-3).Arterioscler Thromb Vasc Biol,2017(116):308905.
[19]张小艺,郑宏,王永强,等.梓醇外泌体对低血清培养致人神经母细胞瘤(SH-SY5Y)细胞损伤的保护作用[J].环球中医药,2017,10(2):155-158.
[20]WEI Y,LI M Z,CUI S F,et al.Shikonin Inhibits the Proliferation of Human Breast Cancer Cells by Reducing Tumor-Derived Exosomes[J].Molecul,2016,21(6):1-10.
[21]王彬辉,高晓宇,章文红,等.姜黄素抗肿瘤作用新剂型及其衍生物研究新进展[J].中国中医药科技,2015,22(2):232-235.
[22]李伟锋,蒋建兰.姜黄素药理作用的研究现状[J].中国临床药理学杂志,2017,33(10):957-960.
[23]SUN D,ZHUANG X,XIANG X,et al.A novel nanoparticle drug delivery system:the anti-Inflammatory activity of curcumin is enhanced when encapsulated in exosomes[J].Mol Ther,2010(18):1606-1614.
[2]袁鹏,郭晓辰,张军平,等.外泌体作为中药载体的研究进展[J].药学学报,2017,52(11):1667-1672.
[3]JOHNSTONE R M.Maturation of reticulocytes:formation of exosomes as a mechanism for shedding membrane proteins[J].Biochem Cell Bio,1992,70(3-4):179-90.
[4]MALIK Z A,KOTT K S,POE A J,et al.Cardiac myocyte exosomes:stability,HSP60,and proteomics[J].Am J Phy Heart Cir Phys,2013,304(7):954-65.
[5]JENJAROENPUN P,KREMENSKA Y,NAIR V M,et al.Characterization of RNA in exosomes secreted by human breast cancer cell lines using next-generation sequencing[J].Peer J,2013(1):e201.
[6]BATRAKOVA E V,KIM M S.Using exosomes,naturallyequipped nanocarriers,for drug delivery[J].J Control Release,2015(219):396-405.
[7]WIKLANDER O P,NORDIN J Z,O’LOUGHLIN A,et al.Extracellular vesicle in vivo biodistribution is determined by cell source,route of administration and targeting[J].JExtracell Vesicles,2015(20):1-13.
[8]张亚飞,王瑜,魏良君.外泌体在精准医疗中的应用潜力[J].生物产业技术,2018(2):65-75.
[9]TAVERNA S,AMODEO V,SAIEVA L,et al.Exosomal shuttling of miR-126 in endothelial cells modulates adhesive and migratory abilities of chronic myelogenous leukemia cells[J].Mol Cancer,2014(13):169.
[10]CAMUSSI G,DEREGIBUS M C,BRUNO S,et al.Exosomes/microvesicles as amechanism of cell-to-cell communication[J].Kidney International,2010,78(9):838-848.
[11]曾维凯,陈建英.外泌体治疗心肌梗死及其相关信号通路的研究进展[J].广东医学,2016,37(21):3295-3297.
[12]LEE M J,PARK D H,KANG J H.Exosomes as the source of biomarkers of metabolic diseases[J].Ann Pediatr Endocrinol Metab,2016,21(3):119-125.
[13]HOEFER I E,STEFFENS S,ALA-KORPELA M,et al.Novel methodologies for biomarker discovery in atherosclerosis[J].Eur Heart J,2015,36(39):2635-2642.
[14]KUWABARA Y,ONO K,HORIE T,et al.Increased microRNA-1 and microRNA-133a levels in serum of patients with cardiovascular disease indicate myocardial damage[J].Circ Cardiovasc Genet,2011,4(4):446-454.
[15]HORSTMAN L L,JY W,JIMENEZ J J,et al.Endothelial microparticles as markers of endothelial dysfunction[J].Front Biosci,2004(9):1118-1135.
[16]SADALLAH S,EKEN C,MARTIN P J,et al.Microparticles(ectosomes)shed by stored human platelets downregulate macrophages and modify the development of dendritic cells[J].Journal of Immunology,2011,186(11):6543-6552.
[17]MA J,ZHAO Y,SUN L,et al.Exosomes derived from Aktmodifed human umbilical cord mesenchymal stem cells improve cardiac regeneration and promote angiogenesis via activating platelet-derived growth factor D[J].Stem CellsTransl Med,2017,6(1):51-59.
[18]ZHU L P,ZHOU J P,ZHANG J X,et al.MiR-15b-5p regulates collateral artery formation by targeting AKT3(protein kinase B-3).Arterioscler Thromb Vasc Biol,2017(116):308905.
[19]张小艺,郑宏,王永强,等.梓醇外泌体对低血清培养致人神经母细胞瘤(SH-SY5Y)细胞损伤的保护作用[J].环球中医药,2017,10(2):155-158.
[20]WEI Y,LI M Z,CUI S F,et al.Shikonin Inhibits the Proliferation of Human Breast Cancer Cells by Reducing Tumor-Derived Exosomes[J].Molecul,2016,21(6):1-10.
[21]王彬辉,高晓宇,章文红,等.姜黄素抗肿瘤作用新剂型及其衍生物研究新进展[J].中国中医药科技,2015,22(2):232-235.
[22]李伟锋,蒋建兰.姜黄素药理作用的研究现状[J].中国临床药理学杂志,2017,33(10):957-960.
[23]SUN D,ZHUANG X,XIANG X,et al.A novel nanoparticle drug delivery system:the anti-Inflammatory activity of curcumin is enhanced when encapsulated in exosomes[J].Mol Ther,2010(18):1606-1614.