Additive effect of nitric oxide and prostaglandin-E(2) synthesis inhibitors in endotoxin-induced uveitis in the rabbit
Additive effect of nitric oxide and prostaglandin-E(2) synthesis inhibitors in endotoxin-induced uveitis in the rabbit
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DOI：
10.1007/bf02285162
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发表时间：
1996-04-01
影响因子：
6.7
通讯作者：
Orts, A
中科院分区：
文献类型：
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作者：
Bellot, JL;Palmero, M;Orts, A
在兔玻璃体内注射内毒素（脂多糖，LPS，10 ng）诱导的眼内炎症模型中研究一氧化氮（NO）和前列腺素E（2）（PGE（2））的参与情况。测定葡萄膜炎的严重程度、虹膜睫状体中的髓过氧化物酶（MPO）活性以及房水中的蛋白质浓度。通过房水中亚硝酸盐和PGE(2)水平分别评估一氧化氮合酶(NOS)和环氧合酶(COX)活性。将 NOS 抑制剂（N-G-硝基-L-精氨酸甲酯，L-NAME，50 mg/kp i.p.）或 COX（双氯芬酸，30 μg，局部）单独或联合治疗与盐水治疗组进行比较。单独使用双氯芬酸或L-NAME可减轻或延缓葡萄膜炎的强度，并部分降低房水中的蛋白质浓度； MPO 活性表明，双氯芬酸（而非 L-NAME）部分减少了虹膜睫状体中多形核白细胞的浸润。两种抑制剂联合治疗可减轻临床葡萄膜炎、血水屏障的破坏以及虹膜睫状体中的 MPO 活性。我们得出结论，NO 和 PGE(2) 对内毒素诱发的兔葡萄膜炎具有相加作用，并且抑制这两种途径将改善葡萄膜炎的治疗管理。
The involvement of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) was investigated in a model of intraocular inflammation induced by intravitreal injection of endotoxin (lipopolysaccharide, LPS, 10 ng) in rabbits. The severity of uveitis, the myeloperoxidase (MPO) activity in iris-ciliary body, and the protein concentration in aqueous humor were determined. Nitric oxide synthase (NOS) and cyclooxygenase (COX) activities were assessed respectively by nitrite and PGE(2) levels in aqueous humor. Treatment with inhibitors of NOS (N-G-nitro-L-arginine methyl ester, L-NAME, 50 mg/kp i.p.) or COX (diclofenac, 30 mu g, topically), alone or in combination, were compared to a saline-treated group. Diclofenac or L-NAME alone reduced or delayed the intensity of uveitis, and partially decreased the protein concentration in aqueous humor; diclofenac, but not L-NAME, partially reduced the polymorphonuclear leukocyte infiltration in the iris ciliary body as indicated by the MPO activity. Treatment with both inhibitors in combination diminished the clinical uveitis, the disruption of the blood-aqueous barrier and the MPO activity in the iris-ciliary body. We conclude that NO and PGE(2) have additive effects in endotoxin-induced uveitis in rabbits, and that the inhibition of both pathways would improve the therapeutical management of uveitis.