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莫西多明对大鼠眼部放疗诱导的视网膜病变和氧化应激的影响。

Effects of Molsidomine on Retinopathy and Oxidative Stress Induced by Radiotheraphy in Rat Eyes.

作者信息

Özer Murat Atabey, Polat Nihat, Özen Serkan, Parlakpınar Hakan, Ekici Kemal, Polat Alaaddin, Vardı Nigar, Tanbek Kevser, Yildiz Azibe

机构信息

a Department of Ophthalmology, Medical Faculty , Giresun University , Giresun , Turkey.

b Department of Ophthalmology, Medical Faculty , Inonu University , Malatya , Turkey.

出版信息

Curr Eye Res. 2017 May;42(5):803-809. doi: 10.1080/02713683.2016.1238943. Epub 2016 Nov 29.

DOI:10.1080/02713683.2016.1238943
PMID:27897441
Abstract

PURPOSE

To determine the role of Molsidomine in preventing radiation-induced retinopathy after head and neck region irradiation of rats with a single radiation dose of 15 Gy.

MATERIALS AND METHODS

Male Wistar albino rats were randomly grouped into five as follows: (1) control group rats, which were applied through an intraperitoneal (i.p.) vehicle without radiotherapy (RT); (2) RT group rats received a single dose of 15 Gy irradiation and after daily 0.1 ml vehicle i.p. for 5 consecutive days; (3) molsidomine (MOL) group rats were treated for 5 consecutive days by i.p. with 4 mg/kg/day MOL; (4) irradiation plus MOL group (RT+MOL) rats received irradiation and after 10 days single daily i.p. dose of MOL for 5 consecutive days; and (5) MOL+RT group rats were treated for 5 consecutive days by i.p. with MOL before RT. At the end of the work the rats were sacrificed under high-dose anesthesia on the 16 day and then eye tissues were taken for histopathological, immunohistochemical (caspase-3), and biochemical analyses (superoxide dismutase [SOD], glutathione peroxidase [GSH], and malondialdehyde [MDA]).

RESULTS

RT significantly decreased both the content of GSH and the activity of SOD, and significantly increased the production of MDA level in the rat eyes. MOL treatment significantly increased the SOD and GSH levels and significantly decreased the MDA production (p < 0.0001). In addition, RT significantly increased the number of ganglion cells (GCs; p = 0.001), whereas especially pretreatment with MOL improved (p = 0.013). RT led to significant retinopathy formation, and MOL therapy protected the retina from radiation-induced retinopathy (p < 0.0001).

CONCLUSIONS

We suggest that MOL is a powerful antioxidant and free radical scavenger that prevents the rat eyes from radiation-induced retinopathy and oxidative stress.

摘要

目的

确定莫索尼定在预防单次辐射剂量为15 Gy的大鼠头颈部照射后放射性视网膜病变中的作用。

材料与方法

雄性Wistar白化大鼠随机分为五组,如下:(1)对照组大鼠,经腹腔注射赋形剂,未接受放射治疗(RT);(2)RT组大鼠接受单次15 Gy照射,然后连续5天每天腹腔注射0.1 ml赋形剂;(3)莫索尼定(MOL)组大鼠连续5天腹腔注射4 mg/kg/天的MOL;(4)照射加MOL组(RT+MOL)大鼠接受照射,10天后连续5天每天单次腹腔注射MOL;(5)MOL+RT组大鼠在RT前连续5天腹腔注射MOL。实验结束时,于第16天在高剂量麻醉下处死大鼠,然后取眼组织进行组织病理学、免疫组织化学(半胱天冬酶-3)和生化分析(超氧化物歧化酶[SOD]、谷胱甘肽过氧化物酶[GSH]和丙二醛[MDA])。

结果

RT显著降低大鼠眼中GSH的含量和SOD的活性,并显著增加MDA水平的产生。MOL治疗显著增加SOD和GSH水平,并显著降低MDA的产生(p < 0.0001)。此外,RT显著增加神经节细胞(GCs)的数量(p = 0.001),而尤其是MOL预处理有所改善(p = 0.013)。RT导致显著的视网膜病变形成,而MOL治疗可保护视网膜免受放射性视网膜病变的影响(p < 0.0001)。

结论

我们认为MOL是一种强大的抗氧化剂和自由基清除剂,可防止大鼠眼睛发生放射性视网膜病变和氧化应激。

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