Human Umbilical Cord MSC-Derived Exosomes Suppress the Development of CCl(4)-Induced Liver Injury through Antioxidant Effect.
Human Umbilical Cord MSC-Derived Exosomes Suppress the Development of CCl(4)-Induced Liver Injury through Antioxidant Effect.
复制标题
人脐带 MSC 衍生的外泌体通过抗氧化作用抑制 CCl4 诱导的肝损伤的发展
DOI：
10.1155/2018/6079642
复制
发表时间：
2018
影响因子：
4.3
通讯作者：
Yan Y
中科院分区：
文献类型：
--
作者：
Jiang W;Tan Y;Cai M;Zhao T;Mao F;Zhang X;Xu W;Yan Z;Qian H;Yan Y
骨髓间充质干细胞（Mesenchymal stem cells，MSCs）已越来越多地应用于临床治疗。外泌体是由不同类型的细胞释放的小（直径30-100 nm）膜囊泡，并且具有与其衍生细胞相似的功能。人脐带间充质干细胞来源的外泌体（Human umbilical cord MSC-derived exosomes，hucMSC-Ex）在肝脏修复中发挥重要作用。然而，hucMSC-Ex对肝损伤发展的影响和机制仍然是难以捉摸的。通过四氯化碳（CCl 4）注射诱导急性和慢性肝损伤和肝肿瘤的小鼠模型，随后通过尾静脉施用hucMSC-Ex。测定hucMSC-Ex对肝损伤的减轻作用。我们进一步探讨了肝损伤发展过程中氧化应激和细胞凋亡的产生，并比较了hucMSC-Ex与常用的肝保护剂联苯双酯（DDB）在肝损伤中的抗氧化作用。hucMSC-Ex可减轻CCl 4诱导的急性肝损伤和肝纤维化，抑制肝肿瘤的生长。在hucMSC-Ex处理的小鼠模型和肝细胞中发现氧化应激和细胞凋亡减少。与联苯双酯（DDB）处理相比，hucMSC-Ex表现出更明显的抗氧化和肝保护作用。hucMSC-Ex可能通过抗氧化潜力抑制CCl 4诱导的肝损伤发展，并且在CCl 4诱导的肝肿瘤发展中可能是比DDB更有效的抗氧化剂。
Mesenchymal stem cells (MSCs) have been increasingly applied into clinical therapy. Exosomes are small (30–100 nm in diameter) membrane vesicles released by different cell types and possess the similar functions with their derived cells. Human umbilical cord MSC-derived exosomes (hucMSC-Ex) play important roles in liver repair. However, the effects and mechanisms of hucMSC-Ex on liver injury development remain elusive. Mouse models of acute and chronic liver injury and liver tumor were induced by carbon tetrachloride (CCl4) injection, followed by administration of hucMSC-Ex via the tail vein. Alleviation of liver injury by hucMSC-Ex was determined. We further explored the production of oxidative stress and apoptosis in the development of liver injury and compared the antioxidant effects of hucMSC-Ex with frequently used hepatic protectant, bifendate (DDB) in liver injury. hucMSC-Ex alleviated CCl4-induced acute liver injury and liver fibrosis and restrained the growth of liver tumors. Decreased oxidative stress and apoptosis were found in hucMSC-Ex-treated mouse models and liver cells. Compared to bifendate (DDB) treatment, hucMSC-Ex presented more distinct antioxidant and hepatoprotective effects. hucMSC-Ex may suppress CCl4-induced liver injury development via antioxidant potentials and could be a more effective antioxidant than DDB in CCl4-induced liver tumor development.