中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (12): 1990-1999.doi: 10.4103/1673-5374.221155

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

骨髓间充质干细胞可减轻NaNO2诱导的缺氧性脑损伤

  

  • 收稿日期:2017-11-01 出版日期:2017-12-15 发布日期:2017-12-15

Bone marrow-derived mesenchymal stem cells ameliorate sodium nitrite-induced hypoxic brain injury in a rat model

Elham H.A. Ali1, Omar A. Ahmed-Farid2, Amany A. E. Osman1   

  1. 1 Faculty of Women for Art, Sciences and Education, Ain Shams University, Cairo, Egypt
    2 National Organization for Drug Control and Research (NODCAR), Giza, Egypt
  • Received:2017-11-01 Online:2017-12-15 Published:2017-12-15
  • Contact: Omar A. Ahmed-Farid, Ph.D.,ebntaimya@yahoo.com.

PDF

282

摘要：

 亚硝酸钠（NaNO2）是化学工业广泛使用的无机盐，其可使血液中正常携氧的低铁血红蛋白氧化成高铁血红蛋白，可引起脑组织缺氧。多能干细胞骨髓间充质干细胞（MSC）移植可促进脑损伤的恢复。为研究骨髓间充质干细胞对NaNO2诱导的缺氧性脑损伤的作用及机制。实验将大鼠随机分为7组，每组12只：对照组，治疗3周和6周；缺氧组（HP）皮下注射NaNO2（35mg/kg）3周诱导缺氧性脑损伤；缺氧恢复组，皮下注射NaNO2（35mg/kg）2和3周诱导缺氧性损伤后，任大鼠自行恢复4和3周；干细胞治疗组，皮下注射NaNO2（35mg/kg）2周诱导缺氧性损伤后，尾静脉一次性注射2×106个骨髓间充质干细胞，再任大鼠自行恢复4周（N-2wSC组）或再皮下注射NaNO21周后再任其自行恢复3周（N-3wSC组）。以HPLC法检测大鼠额叶皮质和中脑神经递质去甲肾上腺素、多巴胺、5-羟色胺和能量物质一磷酸腺苷、二磷酸腺苷、三磷酸腺苷含量，以及反映氧化应激损伤水平标志物的丙二醛、一氧化氮、羟基脱氧鸟苷、还原型和氧化型谷胱甘肽含量。同时对大鼠大脑组织进行HE染色，以观察其病理学改变。结果显示，与HP组比较，骨髓间充质干细胞治疗组缺氧模型大鼠脑组织病理学改变明显减轻，大脑皮质和中脑丙二醛、一氧化氮、氧化型谷胱甘肽和8-羟基-2'-脱氧鸟苷，以及除皮质多巴胺外的单胺类神经递质明显降低，谷胱甘肽，三磷酸腺苷及其比例明显升高。说明骨髓间充质干细胞可通过发挥抗氧化作用，提高大脑的能量供给，对NaNO2诱导的缺氧性脑损伤发挥神经保护作用。

 

orcid:0000-0002-1020-5777(Omar A. Ahmed-Farid)

关键词: 神经再生, 缺氧, 骨髓间充质干细胞, 亚硝酸钠, 单胺类神经递质, 细胞能量

Abstract:

Sodium nitrite (NaNO2) is an inorganic salt used broadly in chemical industry. NaNO2 is highly reactive with hemoglobin causing hypoxia. Mesenchymal stem cells (MSCs) are capable of differentiating into a variety of tissue specific cells and MSC therapy is a potential method for improving brain functions. This work aims to investigate the possible therapeutic role of bone marrow-derived MSCs against NaNO2 induced hypoxic brain injury. Rats were divided into control group (treated for 3 or 6 weeks), hypoxic (HP) group (subcutaneous injection of 35 mg/kg NaNO2 for 3 weeks to induce hypoxic brain injury), HP recovery groups N-2wR and N-3wR (treated with the same dose of NaNO2 for 2 and 3 weeks respectively,followed by 4-week or 3-week self-recovery respectively), and MSCs treated groups N-2wSC and N-3wSC (treated with the same dose of NaNO2 for 2 and 3 weeks respectively, followed by one injection of 2 × 106 MSCs via the tail vein in combination with 4 week self-recovery or intravenous injection of NaNO2 for 1 week in combination with 3 week self-recovery). The levels of neurotransmitters (norepinephrine,dopamine, serotonin), energy substances (adenosine monophosphate, adenosine diphosphate, adenosine triphosphate), and oxidative stress markers (malondialdehyde, nitric oxide, 8-hydroxy-2′-eoxyguanosine,glutathione reduced form, and oxidized glutathione) in the frontal cortex and midbrain were measured using high performance liquid chromatography. At the same time, hematoxylin-eosin staining was performed to observe the pathological change of the injured brain tissue. Compared with HP group, pathological change of brain tissue was milder, the levels of malondialdehyde, nitric oxide, oxidized glutathione, 8-hydroxy-2′-deoxyguanosine, norepinephrine, serotonin, glutathione reduced form, and adenosine triphosphate in the frontal cortex and midbrain were significantly decreased, and glutathione reduced form/oxidized glutathione and adenosine onophosphate/adenosine triphosphate ratio were significantly increased in the MSCs treated groups. These findings suggest that bone marrow-derived MSCs exhibit neuroprotective effects against NaNO2-induced hypoxic brain injury through exerting anti-oxidative effects and providing energy to the brain.

Key words: nerve regeneration, hypoxia, bone marrow-derived mesenchymal stem cells, sodium nitrite, monoamine neurotransmitter, cell energy, neural regeneration