如果角膜不慎被濃鹼燒傷，怎么辦？當然應該立刻用水沖洗。如果處理不當，很容易出現角膜損傷并容易出現血管增生，影響患者視力。最新來自日本學者的研究給我們提供了新的可能手段，可以用含氫氣水反復滴眼睛，這樣能避免血管增生，保護視力。
剛剛看到來自日本慶應義塾大學 - Keio University學者Miyuki Kubota關于氫氣在角膜堿水燒傷中保護作用的研究。該研究采用上皮細胞基因SOD-1缺陷小鼠，通過角膜涂抹氫氧化鈉制
備角膜鹼燒傷模型，備角膜鹼燒傷后發生一系列改變，比較惡劣的后果是在角膜上長出血管，正常角膜沒有血管，這樣才能保證光線的無障礙通過，如果長了血管，
角膜不能完全透光，就會導致視力下降，甚至視力完全消失。角膜血管增生的一個可能機制是角膜受到損傷后，局部活性氧增加，活性氧通過增強NFkb的基因轉錄作用，使內皮細胞血管生長因子（VEGF）增加，活性增強，促進血管增生。因此可以采用ROS清除方法，或抑制NFkb方法達到預防角膜血管增生的目的。本研究發現，采用ROS清除藥物NAC和NFkb抑制劑DHMEQ可以實現預防角膜血管增生的目的，這類研究過去已經有過。本研究真正吸引人的地方應該是采用含氫氣水滴眼睛同樣能實現預防角膜血管增生的目的。
眼睛無論是角膜，還是視網膜，血管增生都是十分麻煩的病理過程，這個研究很容易讓人聯想到，氫氣是否也具有抑制視網膜血管增生的作用。當然晶狀體變不透明的白內障也是可以從這個思路來延伸的。
我的聯想：這個研究還讓我想到1975年曾經有人在《科學》上發表論文，證明呼吸氫氣能治療惡性腫瘤，實體腫瘤一個非常重要的治療手段是設法抑制血管的增生，例如使用VEGF受體單抗。現在這個研究發現氫氣也能抑制血管增生，那么氫氣治療腫瘤的研究也就可以從這個角度來考慮了。
“任何事情都有兩面性”，血管增生對眼睛和腫瘤是壞事情，但對缺血性疾病，例如腦中風、心機梗死、糖尿病肢體壞死等確實好事情，氫氣對這些疾病也有好處，那么對這些疾病的血管增生是什么影響？是促進，還是抑制。這又是一個棘手的問題。
看來事情不是那么簡單，從這個研究看，作者是把氫氣作為類似NAC的作用，抑制或清除能引起血管增生的超氧陰離子（SOD可清除它）或亞硝酸陰離子（超氧陰離子與NO可以產生它），而太田07年的文章證明這兩個物質不能與氫氣直接發生中和反應，那么氫氣又是如何發揮作用的？氫氣的信號作用早就被人提到，現在的研究是否也可以作用氫氣影響信號作用的證據之一。
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).
