Superoxide anion radical as an indirect mediator in ocular inflammatory disease.
Superoxide anion radical as an indirect mediator in ocular inflammatory disease.
复制标题
超氧阴离子自由基作为眼部炎症疾病的间接介质。
作者：
T. Sery;R. Petrillo
无论有没有兔血浆，玻璃体内注射黄嘌呤氧化酶和黄嘌呤的超氧化物生成反应混合物，都被证明是色素和白化兔强烈的葡萄膜和视网膜炎症的媒介。用或不用兔血浆或单独用血浆对热灭活的黄嘌呤氧化酶进行对照，对眼组织没有影响。单独使用黄嘌呤作为对照，几乎没有或几乎没有炎症反应。单独或与兔血浆对照，可产生非常强烈的炎症反应，这可能代表与内源性黄嘌呤的酶反应。玻璃体内注射超氧化物歧化反应混合物后，反应在16h内开始于眼前段，2d后达到高峰。后段的反应延迟，至少在24小时后才明显，可能是由于前房靠近睫状突，细胞渗出首先出现在睫状突。前段葡萄膜炎在4天后开始消退，但后段炎症持续6天以上，在许多情况下，导致视网膜炎和视网膜脱离。超氧化物歧化酶在体外可以有效地抑制反应混合物中的超氧化物，但在体内并不能阻止炎症反应，因为它在眼组织中被发现具有强烈的毒性。氧的其他自由基，以及过氧化氢，可以随着超氧化物的分解而发展，并导致组织损伤。已知的超氧化物将血浆前体转化为中性粒细胞趋化因子的能力，也可能通过积累中性粒细胞在原位产生超氧化物。由于吞噬细胞是超氧化物歧化的潜在来源，本研究为研究氧自由基在眼炎性疾病中的作用提供了良好的实验模型。
Intravitreal injection of a superoxide-generating reaction mixture of xanthine oxidase and xanthine, either with or without rabbit plasma, was shown to be a mediator of an intense uveal and retinal inflammation in pigmented and albino rabbits. Controls of heat-inactivated xanthine oxidase with or without rabbit plasma, or plasma by itself, was without effect on ocular tissues. Xanthine alone as a control exhibited little or no inflammatory response. Controls of active xanthine oxidase by itself, or with rabbit plasma, produced a very strong inflammatory response that may represent enzymic reaction with endogenous xanthine. When the superoxide generating reaction mixture was given intravitreally the reaction began in the anterior segment within 16 hours and reached its peak after 2 days. The response in the posterior segment was delayed and did not become evident until after at least 24 hours, and may be due to the close proximity of the anterior chamber to the ciliary processes where cellular exudates first appear. Anterior segment uveitis began to recede after 4 days but posterior segment inflammation persisted beyond 6 days, and in many instances, led to retinitis, and retinal detachment. Superoxide dismutase was effectively used in vitro to quench superoxide in the reaction mixture but it did not prevent inflammatory reactions in vivo because it was found to possess strong toxic qualities of its own in ocular tissues. Other free radicals of oxygen, as well as hydrogen peroxide, can develop with the breakdown of superoxide, and cause tissue damage. A known ability of superoxide to convert a plasma precursor into a factor chemotactic for neutrophils may also cause superoxide production in situ by accumulating neutrophils. Because phagocytes are potential sources of superoxide, this study provides a good experimental model for studying the influence of oxygen free radicals in ocular inflammatory disease.