Tilton R G, Chang K, Corbett J A, Misko T P, Currie M G, Bora N S, Kaplan H J, Williamson J R
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri.
Invest Ophthalmol Vis Sci. 1994 Jul;35(8):3278-88.
These experiments were undertaken to assess the role of increased nitric oxide production in the pathogenesis of vascular dysfunction associated with endotoxin-induced uveitis.
Lipopolysaccharides (LPS) (100 micrograms of Salmonella minnesota) was injected into foot-pads of Lewis rats randomly assigned to an untreated group or to a group treated with subcutaneous injections of aminoguanidine, a selective inhibitor of the inducible isoform of nitric oxide synthase (iNOS). Controls included untreated and aminoguanidine-treated rats. Twenty to 24 hours later, blood flow and vascular 125I-albumin permeation were quantified in ocular tissues. Eyes were graded histologically for leukocyte infiltration into the anterior uvea and anterior chamber, and leukocyte counts were performed on aqueous fluid. Plasma nitrate levels were measured fluorometrically after enzymatic reduction to nitrite.
Lipopolysaccharides markedly increased plasma nitrate levels and 125I-albumin permeation in aqueous fluid, retina, anterior uvea, and choroid-sclera. Blood flow was increased only in the anterior uvea. Aminoguanidine normalized plasma nitrate levels and prevented or significantly ameliorated the 125I-albumin permeation and blood flow changes in ocular tissues. The increased aqueous fluid content of lymphocytes and neutrophils in LPS-treated rats, as well as the increased histologic score of iritis, were significantly reduced by aminoguanidine.
These results suggest that the hemodynamic and vascular permeability changes associated with endotoxin-induced uveitis are mediated in large part by increased production of nitric oxide.
进行这些实验以评估一氧化氮生成增加在内毒素诱导性葡萄膜炎相关血管功能障碍发病机制中的作用。
将脂多糖（100微克明尼苏达沙门氏菌）注入随机分配至未治疗组或皮下注射氨基胍（一种一氧化氮合酶诱导型同工酶的选择性抑制剂）治疗组的Lewis大鼠足垫。对照组包括未治疗和氨基胍治疗的大鼠。20至24小时后，对眼组织中的血流和血管125I-白蛋白渗透进行定量。对眼睛进行组织学分级，以评估白细胞向前葡萄膜和前房的浸润情况，并对房水进行白细胞计数。在酶促还原为亚硝酸盐后，用荧光法测量血浆硝酸盐水平。
脂多糖显著增加了血浆硝酸盐水平以及房水、视网膜、前葡萄膜和脉络膜-巩膜中的125I-白蛋白渗透。仅前葡萄膜的血流增加。氨基胍使血浆硝酸盐水平恢复正常，并预防或显著改善了眼组织中的125I-白蛋白渗透和血流变化。氨基胍显著降低了脂多糖处理大鼠房水中淋巴细胞和中性粒细胞含量的增加以及虹膜睫状体炎组织学评分的增加。
这些结果表明，与内毒素诱导性葡萄膜炎相关的血流动力学和血管通透性变化在很大程度上是由一氧化氮生成增加介导的。
