Bone marrow mesenchymal stem cells ameliorate hepatic ischemia/reperfusion injuries via inactivation of the MEK/ERK signaling pathway in rats
Bone marrow mesenchymal stem cells ameliorate hepatic ischemia/reperfusion injuries via inactivation of the MEK/ERK signaling pathway in rats
复制标题
骨髓间充质干细胞通过灭活 MEK/ERK 信号通路改善大鼠肝脏缺血/再灌注损伤
DOI：
10.1016/j.jss.2012.04.070
复制
发表时间：
2012-12-01
影响因子：
2.2
通讯作者：
Chen, Gui-hua
中科院分区：
文献类型：
--
作者：
Pan, Guo-zheng;Yang, Yang;Chen, Gui-hua
背景资料：肝移植术后移植物功能障碍或无功能是严重的临床问题，通常由缺血/再灌注损伤（IRI）引起。虽然骨髓间充质干细胞（MSCs）已显示出巨大的潜力，在细胞治疗IRI在几个器官，其机制（S）由MSCs提供的protection.Methods：在本研究中，我们通过尾静脉注射MSCs在70%的肝IRI大鼠模型和测量的生化和病理变化，以评估MSC移植的治疗效果。同时，采用H_2O_2体外模拟氧化损伤并诱导人正常肝细胞株LO_2凋亡的方法，观察骨髓间充质干细胞条件培养液（MSC-CM）对LO_2细胞的保护作用。体外实验表明，MSC-CM促进肝细胞增殖，并对H2 O2诱导的肝细胞凋亡有直接的抑制作用。此外，我们证明，MEK/ERK通路激活的预防发挥了关键作用的protection.Conclusions：这些数据表明，MSC可能是一个潜在的治疗策略，以减轻肝移植后肝缺血/再灌注损伤通过灭活的MEK/ERK信号通路。(C)2012 Elsevier Inc. All rights reserved.
Background: Primary graft dysfunction or nonfunction after liver transplantation, which is usually caused by ischemia/reperfusion injury (IRI), is a serious clinical problem. Although bone marrow mesenchymal stem cells (MSCs) have shown great potential in cell therapy for IRI in several organs, the mechanism(s) by which MSCs offer protection is unclear.Methods: In the present study, we injected MSCs systemically via the tail vein in the rat model of 70% hepatic IRI and measured the biochemical and pathologic alterations to evaluate the therapeutic effect of MSC transplantation. Concurrently, H2O2 was used in vitro to mimic oxidative injury and to induce apoptosis in the human normal liver cell line LO2 to evaluate the protective effects of mesenchymal stem cell conditioned medium (MSC-CM) on LO2 cells.Results: The systemic infusion of MSCs led to a significant prevention of liver enzyme release and an improvement in the histology of the acutely injured liver. In vitro assays demonstrated that MSC-CM promoted hepatocyte proliferation and had a direct inhibitory effect on hepatocyte apoptosis induced by H2O2. In addition, we demonstrated that the prevention of MEK/ERK pathway activation played a pivotal role in the protection.Conclusions: These data suggest that MSC may represent a potential therapeutic strategy to alleviate hepatic ischemia/reperfusion injuries after liver transplantation via inactivation of the MEK/ERK signaling pathway. (C) 2012 Elsevier Inc. All rights reserved.