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雷帕霉素抑制糖尿病视网膜病变中的氧化和血管生成介质。

Rapamycin inhibits oxidative and angiogenic mediators in diabetic retinopathy.

作者信息

Ozdemir Gökhan, Kılınç Metin, Ergün Yusuf, Sahin Elif

机构信息

Department of Ophthalmology, Faculty of Medicine, Kahramanmaraş Sütçüimam University, Kahramanmaraş, Turkiye.

Department of Biochemistry, Faculty of Medicine, Kahramanmaraş Sütçüimam University, Kahramanmaraş, Turkiye.

出版信息

Can J Ophthalmol. 2014 Oct;49(5):443-9. doi: 10.1016/j.jcjo.2014.07.003.

DOI:10.1016/j.jcjo.2014.07.003
PMID:25284101
Abstract

OBJECTIVE

To evaluate the role of rapamycin in the prevention of diabetic oxidative stress and the regulation of angiogenic factors.

DESIGN

Experimental animal study.

METHODS

Diabetes was induced in 20 adult male Wistar rats by a single intraperitoneal administration of streptozotocin (60 mg/kg). Rats were randomly assigned into diabetic and rapamycin groups (n = 10). Ten healthy normal adult male rats of same age formed the control group. All groups were followed for 3 months. Rapamycin group received 1 mg/kg rapamycin via orogastric gavage during the last 4 weeks. At the end of 12 weeks, rats were sacrificed and biochemical oxidative stress markers (malondialdehyde and nitrotyrosine), together with vascular endothelial growth factor, hypoxia-inducible factor-1α, and pigment epithelium-derived factor, were measured in the retina. Blood biochemical analyses were also done.

RESULTS

In the diabetic group, retinal malondialdehyde and nitrotyrosine levels were increased in comparison with control and rapamycin groups (p < 0.05). Rapamycin suppressed oxidative stress and showed a beneficial effect. It also decreased all angiomodulator cytokines compared with the diabetic group (p < 0.05). Correspondingly, rapamycin also decreased plasma malondialdehyde levels compared with the diabetic group (p = 0.037).

CONCLUSIONS

Rapamycin may have a protective role against diabetes-induced oxidative retinal injury and may decrease angiomodulator cytokines.

摘要

目的

评估雷帕霉素在预防糖尿病氧化应激及调节血管生成因子方面的作用。

设计

实验动物研究。

方法

通过单次腹腔注射链脲佐菌素(60 mg/kg)诱导20只成年雄性Wistar大鼠患糖尿病。将大鼠随机分为糖尿病组和雷帕霉素组(n = 10)。10只同年龄健康正常成年雄性大鼠作为对照组。所有组均随访3个月。雷帕霉素组在最后4周通过灌胃给予1 mg/kg雷帕霉素。在12周结束时,处死大鼠,检测视网膜中的生化氧化应激标志物(丙二醛和硝基酪氨酸)以及血管内皮生长因子、缺氧诱导因子-1α和色素上皮衍生因子。同时进行血液生化分析。

结果

与对照组和雷帕霉素组相比,糖尿病组视网膜丙二醛和硝基酪氨酸水平升高(p < 0.05)。雷帕霉素可抑制氧化应激并显示出有益作用。与糖尿病组相比,它还降低了所有血管调节细胞因子水平(p < 0.05)。相应地,与糖尿病组相比,雷帕霉素还降低了血浆丙二醛水平(p = 0.037)。

结论

雷帕霉素可能对糖尿病诱导的视网膜氧化损伤具有保护作用,并可能降低血管调节细胞因子水平。

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