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PNAS:缺氧条件下能够减少和逆转Leigh氏综合症导致的神经病变

2017-05-24 MedSci MedSci原创

这项研究确立了通过调整减少氧气的呼吸量可以改善或者逆转神经系统的病变。但是未来如何开发安全和有效的缺氧疗法,仍需要大量工作。

Leigh氏综合症是最常见因为线粒体功能缺陷所引起的小儿疾病。Leigh氏综合症,表现为一种偶发性的亚急性神经变性,患病的幼儿可能在生命的头几年内导致死亡,而且目前为止没有经过验证有效的疗法。在小鼠动物模型中,缺乏Ndufs4蛋白的小鼠会发生类似于Leigh氏综合症的致命性脑病及神经坏死,大概死于出生后的60天。

在最新上线的PNAS杂志上,Michele Ferrari及其同事报导了他们的发现,通过给予缺氧(hypoxia)治疗方法可以在实验小鼠模型上减缓和减轻神经坏死和脑损伤。

在之前的报道中,研究人员我报告说,从早期开始,如果维持呼吸的氧气量为正常的11%,则可以防止神经系统疾病,并且显着改善这些小鼠的生存率。在这项研究报道中,研究人员发现:因为缺少Ndufs4蛋白的小鼠如果暴露于正常的氧气环境中,会在出生后的60天左右死于神经变性和脑坏死。但是经过缺氧治疗的小鼠最终可以存活到出生后的270天,而死因可能来自心脏病。

可惜的是,如果持续维持17%氧气,或者间歇性的缺氧,则对延缓神经坏死无效。在对于晚期脑病的小鼠中进行缺氧治疗后,可以逆转其已建立的神经系统疾病,改善其行动行为,各项生物体征改善,延长存活时间。重要的是,在4周缺氧治疗后,通过核磁共振检测发现,本来的神经组织中的病变发现改善。但是如果小鼠在恢复到正常的氧气含量时,之后的几天内就会死亡。

这项研究确立了通过调整减少氧气的呼吸量可以改善或者逆转神经系统的病变。但是未来如何开发安全和有效的缺氧疗法,仍需要大量工作。

原始出处:
Michele Ferrari et al. Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome. PNAS (2017) May 8, 2017, doi: 10.1073/pnas.1621511114

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    2017-09-29 drwjr
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    2017-05-25 axin012
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    2017-05-24 flysky120

    学习一下知识

    0

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    2017-05-24 明月清辉

    谢谢分享,学习了

    0

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表皮生长因子受体(EGFR)被广泛认为是驱动头颈部鳞状细胞癌(HNSCC)形成的因素之一。使用单克隆抗体抑制EGFR,已经得到了很好的评估。 HNSCCs组织里富含缺氧组织,而缺氧已被证实参与了下调EGFR膜的表达。 研究纳入58例HNSCCs和9例正常/癌症邻近组织,建立一种新的多重免疫荧光和单细胞分割(通过DAPI染色的细胞核)方法,研究组织中EGFR的表达、内源性缺氧标记CA I

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