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Hydrogen saline treatment attenuates hyperoxia-induced retinopathy by inhibition.pdf
本研究来自第二军医大学长海医院眼科赵世红课题组。获悉刚刚被 接受。
氧气是人体必须的物质,但浓度过高可以导致中毒。成年人视网膜对高浓度的氧气耐受能力相对较高,但新生儿,特别是早产儿对高浓度氧特别敏感,由于新生儿不会表达,往往这种严重的病变等到发现视力已经无法恢复。但由于新生儿,特别是早产儿有时候因为各类疾病必须要呼吸高浓度氧气,造成非常矛盾的局面。
氧气的毒性是由于高浓度的氧气可以导致氧化损伤,本质是导致自由基增加,由于氢气抗氧化能力的发现,本研究尝试用氢气来预防这类损伤。研究结果表明,氢气可以对抗高氧视网膜病变。
研究目的:视网膜血管增生和视网膜病变是视网膜毛细血管增生性异常,是导致失明的重要原因。本研究利用高浓度氧诱导的新生小鼠视网膜病变模型,观察氢气生理盐水治疗视网膜病变的效果。方法:新生7天小鼠暴露在75%氧浓度持续到新生12天,氢气生理盐水腹腔注射(5 ml/kg),新生17天,动物处死,用荧光成像和组织学评估视网膜血管增生,VEGF基因表达采用定量PCR和蛋白表达采用免疫荧光组织化学检测,氧化应激用MDA含量表示。结果发现,氢气盐水能降低视网膜血管增生,减少VEGF mRNA表达和蛋白水平,同时减少MDA含量。结果表明,氢气盐水能保护视网膜发生血管增生。
关于眼科疾病的研究,目前已经有关于视网膜缺血、角膜化学烧伤等研究,有人曾发现,滴氢气水对难治性虹膜睫状体炎。
(前葡萄膜炎(anterior uveitis)又名虹膜睫状体炎(iridocyclitis),虹膜发生炎症后常影响睫状体,故临床上单独的虹膜炎或睫状体为是很少见的。常同时发病。前葡萄膜炎又称虹膜睫状体炎,包括虹膜炎、睫状体炎及虹膜睫状体炎。因为虹膜和睫状体在解剖上互相连接,关系密切,且同为虹膜大环供血,因此虹膜和睫状体往往同时发炎。 虹膜睫状体炎是常见的致盲眼病之一,是最常见的一种葡萄膜炎。)这种眼科疾病是一种难治性疾病,属于自身免疫性炎症。推测氢气治疗可能具有比较好的疗效。
个人评价:血管增生对肿瘤和视网膜是不利因素,但对组织缺血来讲,血管增生能有利于组织血液供应,减少组织发生缺血性损伤,氢气最早的效应是发现具有抗氧化,对抗缺血再灌注损伤的作用。本研究发现氢气对血管增生具有控制作用,与早期日本学者发现氢气水对角膜化学烧伤后血管增生的治疗作用有类似的结论。而且,从这个角度考虑,氢气对肿瘤血管增生是否也具有抑制作用,如果有的话,氢气也可以对实体肿瘤,如乳腺、胃、大肠癌等具有一定治疗作用。
Hydrogen Saline Attenuates Hyperoxia Retinopathy
By Decreasing Oxidative Stress
Lina Huanga, Shihong Zhaoa*, Jinhui Wua,John H. Zhangc, Xuejun Sunb*
Department of Ophthalmologya, Changhai Hospital, Second Military Medical University, Shanghai, 200433, PR China; Department of Diving Medicineb, Faculty of Naval Medicine, Second Military Medical University, Shanghai, 200433, PR China; Department of Physiology and Pharmacologyc,Loma Linda University School of Medicine, Loma Linda,California, USA
*Co-Corresponding authors. Fax: 86-021-81873555, 86-021-65492382. E-mail addresses: zhaosh2001@sina.com (S.H. Zhao), sunxjk@hotmail.com (X.J.Sun).
Abstract
Objective: Retinal neovascularization or retinopathy is a proliferative disorder of retinal capillaries and is the primary cause of blindness. This study examined the therapeutic effect of hydrogen saline (H2 saline) on retinopathy in an established hyperoxia-retinopathy mouse pup model. Methods: Mouse pups were exposed to 75% O2 from postnatal day 7 (P7) to P12. Hydrogen saline was administered by peritoneal injection (5 ml/kg) daily for 5 days. At P17, the pups were decapitated and retinal neovascularization was assessed by fluorescence imaging and histopathological examination.
VEGF expression was evaluated by real time PCR and immunofluorescence histochemistry. Oxidative stress was measured by MDA assessment. Results: Hydrogen saline decreased the retinal neovascularization, reduced VEGF mRNA and protein expressions, and suppressed MDA levels. Conclusions:Hydrogen saline might be a potential treatment for hyperoxia-induced retinopathy by inhibition of oxidative stress and reduction of VEGF expression.
Keywords: retinal neovascularization; hyperoxia; hydrogen saline; oxidative stress; VEGF
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