Bellot J L, Palmero M, García-Cabanes C, Espí R, Hariton C, Orts A
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad de Alicante, Spain.
Inflamm Res. 1996 Apr;45(4):203-8. doi: 10.1007/BF02285162.
The involvement of nitric oxide (NO) and prostaglandin E2 (PGE2) 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 PGE2 levels in aqueous humor. Treatment with inhibitors of NOS (NG-nitro-L-arginine methyl ester, L-NAME, 50 mg/kp i.p.) or COX (diclofenac, 30 micrograms, 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 PGE2 have additive effects in endotoxin-induced uveitis in rabbits, and that the inhibition of both pathways would improve the therapeutical management of uveitis.
在兔眼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，研究了一氧化氮（NO）和前列腺素E2（PGE2）的作用。测定了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。分别通过房水中亚硝酸盐和PGE2水平评估一氧化氮合酶（NOS）和环氧化酶（COX）活性。将一氧化氮合酶抑制剂（NG-硝基-L-精氨酸甲酯，L-NAME，50 mg/kg腹腔注射）或环氧化酶抑制剂（双氯芬酸，30 μg，局部用药）单独或联合治疗与生理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；双氯芬酸而非L-NAME可部分降低虹膜睫状体中多形核白细胞浸润，这通过MPO活性得以体现。联合使用两种抑制剂可减轻临床葡萄膜炎、血-房水屏障破坏以及虹膜睫状体中的MPO活性。我们得出结论，NO和PGE2在兔内毒素诱导的葡萄膜炎中具有相加作用，并且抑制这两条途径将改善葡萄膜炎的治疗管理。
