Highly selective inhibitor of inducible nitric oxide synthase enhances S-antigen-induced uveitis.
Highly selective inhibitor of inducible nitric oxide synthase enhances S-antigen-induced uveitis.
复制标题
诱导型一氧化氮合酶的高度选择性抑制剂可增强 S 抗原诱导的葡萄膜炎。
DOI：
10.1076/ceyr.26.1.1.14250
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发表时间：
2003
影响因子：
2
通讯作者：
Rao,Narsing
中科院分区：
文献类型：
--
作者：
Charlotte,Frederic;Ito,Shinji;Wu,Guey;Kimoto,Takashi;Rao,Narsing
目的观察诱导型一氧化氮合酶（inducible nitric oxide synthase，iNOS）抑制剂N-3-氨甲基苄基乙脒（1400 W）对EAU效应期的影响。方法用牛视网膜S抗原致敏16只刘易斯大鼠，其中10只于S抗原致敏后第11 ~ 13天皮下注射1400 W（20 mg/kg），每日3次。10只大鼠中的5只也从第7天至第13天每天两次腹腔注射聚乙二醇修饰的超氧化物歧化酶（SOD 1000 IU）。6只大鼠从第7天至第13天接受生理盐水的腹膜内和/或皮下注射。在第14天摘除眼睛。通过组织学评分评估炎性病变的强度。结果1400 W/SOD组大鼠的组织学评分（26 ± 2.1）高于生理盐水组（20.5 ± 8; p < 0.0001）和1400 W/SOD组（20.5 ± 4.9; p < 0.005）。1400 W处理的大鼠脉络膜（60.7 ± 16.8µm）比生理盐水（19.2 ± 9.4µm，p < 0.0005）或1400 W/SOD处理的大鼠（29.6 ± 19.3µm，p < 0.05）更厚。光感受器层在1400 W处理的大鼠中（8.4 ± 32.1μm）比在盐水-（40 ± 26.7μm; p < 0.05）或1400 W/SOD处理的大鼠中（60.8 ± 38.1μm; p < 0.05）更薄。这意味着iNOS在视网膜外层的表达可能对EAU有保护作用。
PurposeInvestigated the effect of N-3-aminomethylbenzylacetamidine (1400W), a highly selective inhibitor of inducible nitric oxide synthase (iNOS), on the effector phase of EAU.MethodsSixteen Lewis rats were sensitized with bovine retinal S-antigen; ten of them injected subcutaneously with 1400W (20mg/kg) three times a day, from day 11 through day 13 following the injection of S-antigen. Five of the ten rats were also injected intraperitoneally with polyethyleneglycol- modified superoxide dismutase (SOD 1000 IU) twice a day from day 7 through day 13. Six rats received intraperitoneal and/or subcutaneous injections of normal saline from day 7 through day 13. The eyes were enucleated on day 14. The intensity of the inflammatory lesion was assessed by a histological score. The thickness of the choroidal and photoreceptor layers was measured.ResultsThe histological score was higher in the 1400W-treated rats (26 ± 2.1) than in the saline- (20.5 ± 8; p < 0.0001) or 1400 W/SOD-treated rats (20.5 ± 4.9; p < 0.005). The choroid was thicker in the 1400W-treated rats (60.7 ± 16.8µm) than in the saline- (19.2 ± 9.4µm, p < 0.0005) or the 1400 W/SOD-treated rats (29.6 ± 19.3µm, p < 0.05). The photoreceptor layer was thinner in the 1400W-treated rats (8.4 ± 32.1µm) than in the saline- (40 ± 26.7µm; p < 0.05) or 1400 W/SOD-treated rats (60.8 ± 38.1µm; p < 0.05).ConclusionThe data suggests that 1400W exacerbates choroidal inflammation and photoreceptor damage at the effector phase of S-antigen-induced uveitis. This implies that iNOS expressed in the outer retina may have a protective role in EAU.