使用硫辛酸和吲哚美辛治疗视网膜神经变性早期阶段的实验原理

V. Neroev, T. Pavlenko, N. Chesnokova, O. Beznos, T. D. Okhotsimskaya, A. Y. Panova
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引用次数: 0

摘要

目的:评估使用硫辛酸和吲哚美辛锡眼药水治疗早期视网膜神经变性的可能性。研究对象为 20 只栗鼠兔,其中 16 只兔的视网膜神经变性过程是通过静脉注射 6-羟基多巴胺(6-OHDA)产生的,每只眼 0.25 毫克,另外 4 只兔(8 只眼)作为对照。在注射 6-OHDA 后的 7 天内,分别或联合注射 0.5% 的硫辛酸和 0.1% 的吲哚考利,每天 5 次。评估瞳孔光反应并分析眼底情况。测定视网膜匀浆中的α2-巨球蛋白(2-MG)和SOD活性、多巴胺和蛋白质浓度。与未处理组相比,硫辛酸注射液几乎将视网膜损伤面积减少了一半(p d 0.005)。吲哚美辛的效果较差,但两种药物联合使用可最大程度地减少损伤面积(与未处理组相比,p d 0.05)。两种制剂都能使受干扰的瞳孔光反应恢复正常。注射 6-OHDA 会导致视网膜中多巴胺浓度下降(0.050 ± 0.009 pg/mg,而健康对照组为 0.095 ± 0.031 pg/mg,р d 0,05)。在注射吲哚美辛和硫辛酸后,浓度呈上升趋势,而在联合使用这两种药物治疗后,浓度显著增加(0.141 ± 0.037 皮克/毫克,与未经治疗的动物相比,p d 0.01)。注射 6-OHDA 后,视网膜中 2-MG 的活性降低(2.93 ± 0.42 pg/mg,而健康对照组为 5.5 ± 1.2 pg/mg,р < 0 005),而 SOD 的活性降低(健康对照组为 13.30 ± 5.68 U/mg ,未处理动物为 5.41 ± 1.50 U/mg ,р < 0.05)。两种制剂单独使用或混合使用都会导致 2-MG 活性显著增加(硫辛酸 - 4.19 ± 0.91 pg/mg,吲哚美辛 - 6.95 ± 1.09 pg/mg,混合使用 - 7.25 ± 0.63 pg/mg,р < 0.05)和 SOD 活性(硫辛酸 - 8.25 ± 1.27 U/mg, 吲哚美辛 - 29.84 ± 6.63 U/mg, 组合 - 23.99 ± 3.78 U/mg, 与未处理动物相比р < 0.01)。吲哚美辛和硫辛酸的眼药水组合对预防6-OHDA引起的眼损伤最有效,这使得这种方法有望用于治疗伴有神经变性的眼病。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Experimental rationale for the use of thioctic acid and indomethacin in the therapy of the early stage of retinal neurodegeneration
Purpose: to assess the possibility of using thioctic acid and indomethacin tin eyedrops for the therapy of early stages of retinal neurodegeneration.Material and methods. The study was performed on 20 Chinchilla rabbits, including 16 rabbits in whom the neurodegenerative process in the retina was produced by intravitreal installation of 6-hydroxydopamine (6-OHDA), 0.25 mg per eye, and 4 rabbits (8 eyes) served as control. Thioctic acid 0.5% and Indocollir 0.1% were instilled separately and in combination 5 times daily for 7 days after the injection of 6-OHDA. Pupillary light reaction was estimated and eye fundus condition analyzed. Alpha2-macroglobuline ( 2-MG) and SOD activity, dopamine and protein concentrations were measured in retinal homogenates.Results. Instillations of thioctic acid reduced the retinal damage area almost by half as compared to the untreated group (p d 0.005). Indomethacin was less effective, but the combination of the two drugs brought about a maximal reduction of the damage area (p d 0.05 against the untreated group). Both preparations normalized the disturbed pupillary light reaction. The injection of 6-OHDA caused a decrease of dopamine concentration in the retina (0.050 ± 0.009 pg/mg as against 0.095 ± 0.031 pg/mg in healthy controls, р d 0,05). After instillations of indomethacin and thioctic acid, the concentration tended to increase, and it increased significantly after treatment with their combination (0.141 ± 0.037 pg/mg, p d 0.01 as against untreated animals). The activity of 2-MG in retina decreased after a 6-OHDA injection (2.93 ± 0.42 pg/mg as against 5.5 ± 1.2 pg/mg in healthy controls, р < 0 005) just as they increased the decreased SOD (13.30 ± 5.68 U/mg in healthy controls, 5.41 ± 1.50 U/mg in untreated animals, р < 0.05). Both preparations applied separately or in combination caused a significant increase of 2-MG activity (thioctic acid — 4.19 ± 0.91 pg/mg, indomethacin — 6.95 ± 1.09 pg/mg, combination — 7.25 ± 0.63 pg/mg, р < 0.05 as against the untreated animals) and SOD activity (thioctic acid — 8.25 ± 1.27 U/mg, indomethacin — 29.84 ± 6.63 U/mg, combination — 23.99 ± 3.78 U/mg, р < 0.01 as against the untreated animals).Conclusion. The combination of indomethacin and thioctic acid in eyedrops is the most effective for the prevention of eye damage caused by 6-OHDA, which makes this method promising for the treatment of eye diseases accompanied by neurodegeneration.
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