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基于近期临床及病理生理学观察的年龄相关性黄斑变性预防及预防性治疗的一种新的可能策略

[A new possible strategy for prevention and preventive treatment of age-related macular degeneration resting on recent clinical and pathophysiological observations].

作者信息

Fischer Tamás

出版信息

Orv Hetil. 2009 Mar 15;150(11):503-12. doi: 10.1556/OH.2009.28524.

Abstract

The beneficial effect achieved by the treatment of endothelial dysfunction in chronic cardiovascular diseases is already an evidence belonging to the basic treatment of the disease. Given the fact that the vascular system is uniform and consubstantial both physiologically, pathophysiologically and in terms of therapy, and that it plays a key role in age-related macular degeneration (AMD)--a disease leading to tragic loss of vision with its etiology and therapy being unknown--endothelial dysfunction should be treated. The pleiotropic effects of ACE-inhibitors, AR-blockers and statins and third generation beta blockers help to restitute the balance between vasodilators and vasoconstrictors in endothelial dysfunction caused by oxidative stress, the balance of growth factors and their inhibitors, pro- and anti-inflammatory substances and prothrombotic and fibrinolytic factors, inhibit the formation of oxidative stress and its harmful effects; while aspirin with its pleiotropic effects acting as an antiaggregation substance on platelets helps to set the endothelial layer back to its normal balance regarding its vasodilating, antithrombotic, antiadhesive and anti-inflammatory functions; trimetazidine as an adjuvant agent helps to normalize, to restore the disturbed metabolism of the retinal tissue functioning insufficiently, in the end. The angiotensin II receptor blocker telmisartan with its peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist effect inhibits the development of choroidal neovascularisation (CNV) and improves it clinically favourably. The third generation beta adrenergic receptor blocker carvedilol and nebivolol as well as the peroxisome proliferator-activated receptor-gamma agonist pioglitazone elicit their antioxidant vascular protective effects mitochondrially. For the above reasons it is suggested that, as a part of long term primary and/or secondary prevention, the following groups of patients with AMD receive--taking into consideration all possible side effects--ACE-inhibitor and/or AR blocker and statin and aspirin treatment, and trimetazidine as adjuvant medicine, and third generation beta adrenergic receptor blockers: 1. those without macular degeneration but being above the age of 50 and having risk factors inducing endothelial dysfunction; 2. those, who already developed AMD in one eye as a prevention in the second, unaffected eye; and 3. those patients who developed AMD in both eyes in order to ameliorate or merely slow the progression of the disease. Besides, it is advisory and important to eliminate AMD risk factors (cardiovascular risk factors also) inducing oxidative stress with consecutive endothelial dysfunction.

摘要

慢性心血管疾病中内皮功能障碍治疗所取得的有益效果,已然属于该疾病基础治疗的范畴。鉴于血管系统在生理、病理生理以及治疗方面均具有一致性和同源性,且其在年龄相关性黄斑变性(AMD)——一种病因及治疗方法均不明、会导致视力悲惨丧失的疾病——中起着关键作用,因此内皮功能障碍应当予以治疗。血管紧张素转换酶抑制剂(ACE抑制剂)、血管紧张素受体阻滞剂(AR阻滞剂)、他汀类药物以及第三代β受体阻滞剂的多效性作用,有助于恢复因氧化应激所致内皮功能障碍中血管舒张剂与血管收缩剂之间的平衡、生长因子及其抑制剂之间的平衡、促炎和抗炎物质之间的平衡以及血栓形成和纤溶因子之间的平衡,抑制氧化应激的形成及其有害影响;而阿司匹林具有多效性作用,作为血小板抗聚集物质,有助于使内皮细胞层在血管舒张、抗血栓形成、抗黏附及抗炎功能方面恢复至正常平衡状态;曲美他嗪作为辅助药物,最终有助于使功能不足的视网膜组织紊乱的代谢恢复正常。血管紧张素II受体阻滞剂替米沙坦具有过氧化物酶体增殖物激活受体γ(PPAR-γ)激动剂效应,可抑制脉络膜新生血管(CNV)的发展,并在临床上产生有利改善。第三代β肾上腺素能受体阻滞剂卡维地洛和奈必洛尔以及过氧化物酶体增殖物激活受体γ激动剂吡格列酮,在线粒体水平发挥其抗氧化血管保护作用。基于上述原因,建议作为长期一级和/或二级预防的一部分,以下几类AMD患者——考虑到所有可能的副作用——接受ACE抑制剂和/或AR阻滞剂、他汀类药物及阿司匹林治疗,并使用曲美他嗪作为辅助药物,以及第三代β肾上腺素能受体阻滞剂:1. 年龄超过50岁、无黄斑变性但具有诱导内皮功能障碍风险因素的患者;2. 一只眼睛已发生AMD的患者,用于预防另一只未受影响的眼睛;3. 双眼均已发生AMD的患者,以改善或仅仅减缓疾病进展。此外,消除诱导氧化应激继而导致内皮功能障碍的AMD风险因素(也包括心血管风险因素)是建议性且重要的。

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