Medicine, School of Medicine, University of São Paulo - USP, São Paulo 01246-903, SP, Brazil.
Respir Physiol Neurobiol. 2013 Jan 15;185(2):435-45. doi: 10.1016/j.resp.2012.08.015. Epub 2012 Aug 27.
We evaluated the effects of anti-iNOS (1400W - W) associated with leukotriene antagonist (montelukast - M) or corticosteroid (dexamethasone - D) on distal lung of guinea pigs (GP) with chronic pulmonary inflammation.
GP were inhaled with ovalbumin (OVA-2×/week/4 weeks), treated with M (OVAM), D (OVAD) and/or W (OVAW, OVADW, OVAMW) and distal lungs were evaluated by morphometry.
Isolated treatments were not sufficient to reduce all parameters. In OVADW, all parameters were reduced with greater reduction in elastic fibers, TIMP-1, IL-4, IL-5, IFN-gamma and PGF2-alpha compared with OVAD (p<0.05). OVAMW potentiated the reduction of actin, elastic fibers, TIMP-1, IL-4, IL-5, TGF-beta, IFN-gamma, iNOS, and PGF2-alpha to a greater extent than OVAM (p<0.05). A reduction of TIMP-1, IL-4, IL-5, TGF-beta, IFN-gamma and iNOS was observed in OVADW compared with OVAMW (p<0.05).
Although anti-iNOS paired with montelukast or dexamethasone yields better results than isolated treatments, the most effective pairing for controlling inflammation, oxidative stress and remodeling in this asthma model was found to be corticosteroids and anti-iNOS.
我们评估了抗 iNOS(1400W-W)与白三烯拮抗剂(孟鲁司特-M)或皮质类固醇(地塞米松-D)联合应用对慢性肺部炎症的豚鼠(GP)远端肺的影响。
GP 吸入卵白蛋白(OVA-2×/周/4 周),用 M(OVA-M)、D(OVA-D)和/或 W(OVA-W、OVA-DW、OVA-MW)治疗,并通过形态计量学评估远端肺。
单独治疗不足以降低所有参数。在 OVA-DW 中,与 OVA-D 相比,所有参数均降低,弹性纤维、TIMP-1、IL-4、IL-5、IFN-γ和 PGF2-α的减少更为明显(p<0.05)。OVA-MW 比 OVA-M 更能增强肌动蛋白、弹性纤维、TIMP-1、IL-4、IL-5、TGF-β、IFN-γ、iNOS 和 PGF2-α的减少(p<0.05)。与 OVA-MW 相比,OVA-DW 中观察到 TIMP-1、IL-4、IL-5、TGF-β、IFN-γ和 iNOS 的减少(p<0.05)。
尽管抗 iNOS 与孟鲁司特或地塞米松联合应用比单独治疗效果更好,但在这种哮喘模型中,控制炎症、氧化应激和重塑的最有效联合用药是皮质类固醇和抗 iNOS。