如果角膜不慎被浓硷烧伤，怎么办？当然应该立刻用水冲洗。如果处理不当，很容易出现角膜损伤并容易出现血管增生，影响患者视力。最新来自日本学者的研究给我们提供了新的可能手段，可以用含氢气水反复滴眼睛，这样能避免血管增生，保护视力。

刚刚看到来自日本庆应义塾大学 - Keio University学者Miyuki Kubota关于氢气在角膜碱水烧伤中保护作用的研究。该研究采用上皮细胞基因SOD-1缺陷小鼠，通过角膜涂抹氢氧化钠制备角膜硷烧伤模型，备角膜硷烧伤后发生一系列改变，比较恶劣的后果是在角膜上长出血管，正常角膜没有血管，这样才能保证光线的无障碍通过，如果长了血管，角膜不能完全透光，就会导致视力下降，甚至视力完全消失。角膜血管增生的一个可能机制是角膜受到损伤后，局部活性氧增加，活性氧通过增强NFkb的基因转录作用，使内皮细胞血管生长因子（VEGF）增加，活性增强，促进血管增生。因此可以采用ROS清除方法，或抑制NFkb方法达到预防角膜血管增生的目的。本研究发现，采用ROS清除药物NAC和NFkb抑制剂DHMEQ可以实现预防角膜血管增生的目的，这类研究过去已经有过。本研究真正吸引人的地方应该是采用含氢气水滴眼睛同样能实现预防角膜血管增生的目的。

眼睛无论是角膜，还是视网膜，血管增生都是十分麻烦的病理过程，这个研究很容易让人联想到，氢气是否也具有抑制视网膜血管增生的作用。当然晶状体变不透明的白内障也是可以从这个思路来延伸的。

我的联想：这个研究还让我想到1975年曾经有人在《科学》上发表论文，证明呼吸氢气能治疗恶性肿瘤，实体肿瘤一个非常重要的治疗手段是设法抑制血管的增生，例如使用VEGF受体单抗。现在这个研究发现氢气也能抑制血管增生，那么氢气治疗肿瘤的研究也就可以从这个角度来考虑了。

“任何事情都有两面性”，血管增生对眼睛和肿瘤是坏事情，但对缺血性疾病，例如脑中风、心机梗死、糖尿病肢体坏死等确实好事情，氢气对这些疾病也有好处，那么对这些疾病的血管增生是什么影响？是促进，还是抑制。这又是一个棘手的问题。

看来事情不是那么简单，从这个研究看，作者是把氢气作为类似NAC的作用，抑制或清除能引起血管增生的超氧阴离子（SOD可清除它）或亚硝酸阴离子（超氧阴离子与NO可以产生它），而太田07年的文章证明这两个物质不能与氢气直接发生中和反应，那么氢气又是如何发挥作用的？氢气的信号作用早就被人提到，现在的研究是否也可以作用氢气影响信号作用的证据之一。

Hydrogen and N-acetyl-L-cysteine rescue oxidative stress-induced angiogenesis in a mouse corneal alkali-burn model 全文ms

,¹ Shigeto Shimmura,² Shunsuke Kubota,³ Hideyuki Miyashita,⁴ Naoko Kato,⁵ Kousuke Noda,⁶ Yoko Ozawa,⁷ Tomohiko Usui,⁸ Susumu Ishida,⁹ Kazuo Umezawa,¹⁰ Toshihide Kurihara,¹¹ and Kazuo Tsubota¹²

¹Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan ²Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan ³Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan ⁴Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan ⁵Ophthalmology, Keio University School of Medicine, Tokyo, Japan ⁶Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan ⁷Ophthalmology, Keio University School of Medicine, Tokyo, Japan ⁸Ophthalmology, University of Tokyo, Tokyo, Japan ⁹Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan ¹⁰Applied Chemistry, Keio University, Yokohama, Japan ¹¹Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan ¹²Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan

Correspondence: Shigeto Shimmura, Email: shige@sc.itc.keio.ac.jp

Abstract

Purpose: To investigate the role of reactive oxygen species (ROS) as the prime initiators of the angiogenic response following alkali injury of the cornea, and observe the effects of anti-oxidants in preventing angiogenesis.

Methods: The corneal epitheliums of SOD-1 deficient mice (KO) or wild type mice (WT) were removed after applying 0.15N NaOH to establish the animal model of alkali burn. ROS production was semi-quantitatively measured by dihydroethidium (DHE) fluorescence. Angiogenesis was visualized by CD31 immunohistochemistry. The effects of the specific NF- B inhibitor DHMEQ, the antioxidant N-acetyl-L-cysteine (NAC) and hydrogen (H2) solution were observed.

Results: ROS production in the cornea was enhanced immediately after alkali injury as shown by increased dihydroethidium (DHE) fluorescence (p < 0.01). NFkappa B (NF- B) activation and the upregulation of vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1) were significantly enhanced (p < 0.01), leading to a significantly larger area of angiogenesis. Angiogenesis in SOD-1-/- mice corneas were significantly higher in wild type mice (P < 0.01), confirming the role of ROS. Pretreatment with the specific NF- B inhibitor DHMEQ or the antioxidant N-acetyl-L-cysteine (NAC) significantly reduced corneal angiogenesis by down regulating the NF- B pathway (p < 0.01) in both WT and SOD-1-/- mice. Furthermore, we showed that irrigation of the cornea with hydrogen (H2) solution significantly reduced angiogenesis after alkali-burn injury (p < 0.01).

 

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