Protective effects of N-acetyl-L-cysteine in human oligodendrocyte progenitor cells and restoration of motor function in neonatal rats with hypoxic-ischemic encephalopathy.

Protective effects of N-acetyl-L-cysteine in human oligodendrocyte progenitor cells and restoration of motor function in neonatal rats with hypoxic-ischemic encephalopathy.
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DOI:
10.1155/2015/764251
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发表时间:
2015
期刊:
Evidence-based complementary and alternative medicine : eCAM
影响因子:
--
通讯作者:
Kim YB
Kim YB
中科院分区:
其他
文献类型:
--
作者:
Park D;Shin K;Choi EK;Choi Y;Jang JY;Kim J;Jeong HS;Lee W;Lee YB;Kim SU;Joo SS;Kim YB

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目标。鉴于少突胶质前体细胞是新生儿缺氧缺血性脑病的靶细胞,本研究旨在探讨抗氧化剂N-乙酰-L-半胱氨酸对少突胶质前体细胞及新生大鼠的保护作用。方法:研究方法。在体外实验中,通过四甲基偶氮唑盐比色法和细胞凋亡信号分析,观察NAC对KCN对F3细胞毒性的保护作用。在体内实验中,于出生后7d对缺氧缺血手术所致HIE大鼠给予NAC,分析其运动功能和脑白质脱髓鞘情况。结果。NAC可降低KCN对F3细胞的杀伤作用,尤其是通过调节Bcl2和p-ERK抑制细胞的凋亡。给予NAC可恢复新生HIE动物的运动功能,如对侧脑前肢的利用率、运动能力和转杆运动能力。研究还证实,NAC可减轻易受HIE影响的脑白质区域--胼胝体的脱髓鞘。结论。结果表明,NAC通过调节抗细胞凋亡信号,在体内外通过保护OPC发挥神经保护作用,而F3可能是筛选脱髓鞘疾病候选基因的良好工具。
Objective. Since oligodendrocyte progenitor cells (OPCs) are the target cells of neonatal hypoxic-ischemic encephalopathy (HIE), the present study was aimed at investigating the protective effects of N-acetyl-l-cysteine (NAC), a well-known antioxidant and precursor of glutathione, in OPCs as well as in neonatal rats. Methods. In in vitro study, protective effects of NAC on KCN cytotoxicity in F3.Olig2 OPCs were investigated via MTT assay and apoptotic signal analysis. In in vivo study, NAC was administered to rats with HIE induced by hypoxia-ischemia surgery at postnatal day 7, and their motor functions and white matter demyelination were analyzed. Results. NAC decreased KCN cytotoxicity in F3.Olig2 cells and especially suppressed apoptosis by regulating Bcl2 and p-ERK. Administration of NAC recovered motor functions such as the using ratio of forelimb contralateral to the injured brain, locomotor activity, and rotarod performance of neonatal HIE animals. It was also confirmed that NAC attenuated demyelination in the corpus callosum, a white matter region vulnerable to HIE. Conclusion. The results indicate that NAC exerts neuroprotective effects in vitro and in vivo by preserving OPCs, via regulation of antiapoptotic signaling, and that F3.Olig2 human OPCs could be a good tool for screening of candidates for demyelinating diseases.
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