Effect of bone marrow-derived mesenchymal stem cells on endotoxin-induced oxidation of plasma cysteine and glutathione in mice.

Effect of bone marrow-derived mesenchymal stem cells on endotoxin-induced oxidation of plasma cysteine and glutathione in mice.
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DOI:
10.4061/2010/868076
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发表时间:
2010-03-08
影响因子:
4.3
通讯作者:
Rojas M
Rojas M
中科院分区:
医学3区
文献类型:
--
作者:
Iyer SS;Torres-Gonzalez E;Neujahr DC;Kwon M;Brigham KL;Jones DP;Mora AL;Rojas M

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骨髓源性间充质干细胞(bmmdmsc)正在成为包括急性肺损伤(ALI)在内的各种炎症性疾病的治疗方式。炎症的一个标志,也是ALI患者的一致观察,是全身氧化还原环境的扰动。然而,关于BMDMSC对全身氧化还原状态的影响知之甚少。本研究的目的是确定外源性注入BMDMSC是否可以防止内毒素诱导的血浆半胱氨酸(Cys)和谷胱甘肽(GSH)氧化还原状态的氧化。为了确定对BMDMSC氧化还原状态的影响,小鼠腹腔注射内毒素(1 mg/kg),然后静脉输注5 × 105 BMDMSC或等体积的生理盐水溶液。对照组小鼠腹腔注射内毒素,然后静脉注射5 × 105肺成纤维细胞。采用高效液相色谱法测定半胱氨酸、胱氨酸(CySS)、谷胱甘肽(GSH)和谷胱甘肽二硫(GSSG)的浓度。结果显示,BMDMSC输注后,血浆Cys和GSH水平连续保持。数据显示,BMDMSC输注导致更多的还原Cys和GSH氧化还原状态。这些发现首次证明了BMDMSC在体内具有抗氧化作用,并增加了我们对BMDMSC在肺损伤中的全身作用的理解。
Bone marrow-derived mesenchymal stem cells (BMDMSC) are emerging as a therapeutic modality in various inflammatory disease states, including acute lung injury (ALI). A hallmark of inflammation, and a consistent observation in patients with ALI, is a perturbation in the systemic redox environment. However, little is known about the effects of BMDMSC on the systemic redox status. The objective of the present study was to determine whether exogenously infused BMDMSC protect against endotoxin-induced oxidation of plasma cysteine (Cys) and glutathione (GSH) redox states. To determine the effect on the redox state if BMDMSC, mice received endotoxin intraperitoneally (1 mg/kg), followed by intravenous infusion of either 5 × 105 BMDMSC or an equal volume of saline solution. Control mice received intraperitoneal endotoxin followed by 5 × 105 lung fibroblasts given intravenously. Cys, cystine (CySS), GSH, and glutathione disulfide (GSSG) concentrations were determined by HPLC. Results showed sequential preservation of plasma Cys and GSH levels in response to BMDMSC infusion. The data show that BMDMSC infusion leads to a more reducing Cys and GSH redox state. The findings are the first to demonstrate that BMDMSC have antioxidant effects in vivo, and add to our understanding of the systemic effects of BMDMSC in lung injury.
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