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芦丁对糖尿病大鼠视网膜血管内皮生长因子、肿瘤坏死因子-α、醛糖还原酶及总抗氧化能力的影响:分子机制与眼内药代动力学

Effect of rutin on retinal VEGF, TNF-α, aldose reductase, and total antioxidant capacity in diabetic rats: molecular mechanism and ocular pharmacokinetics.

作者信息

Gupta Suresh Kumar, Sharma Hanuman Prasad, Das Ujjalkumar, Velpandian Thirumurthy, Saklani Ravi

机构信息

Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), M.B. Road, Pushp Vihar Sector III, New Delhi, 110017, India.

Ocular Pharmacology and Pharmacy Division, Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India.

出版信息

Int Ophthalmol. 2020 Jan;40(1):159-168. doi: 10.1007/s10792-019-01165-x. Epub 2019 Aug 27.

DOI:10.1007/s10792-019-01165-x
PMID:31456155
Abstract

PURPOSE

The current study was conducted to explore the potential of rutin in preventing sight-threatening diabetic retinopathy.

METHODS

Wistar albino rats (either sex) weighing 200-225 g were intraperitoneally injected with 45 mg/kg streptozotocin (pH 4.5). Rats having blood glucose ≥ 300 mg/dL were divided into two groups (n = 8; each group). Group I served as diabetic control and received normal saline p.o. Group II received rutin 50 mg/kg p.o. for 24 weeks. At the end of 24 weeks, retinal fundus and fluorescein imaging were done, rats were killed, and retinal biochemical assessments were conducted. Moreover, ocular pharmacokinetics of rutin was assessed in the normal rats after a single oral dose of 50 mg/kg.

RESULTS

Rutin treatment significantly (p < 0.001) lowered retinal vascular endothelial growth factor, tumor necrosis factor-α, and aldose reductase. Rutin treatment significantly (p < 0.001) elevated the levels of total antioxidant capacity of the retinas. Fundus examination of rutin-treated group showed significantly lower tortuosity index and normal fluorescein angiography. Rutin was detected in the retina as well as in aqueous humor of normal rats.

CONCLUSION

Rutin treatment significantly arrested the biochemical disturbances of diabetic retinopathy. The distribution of orally ingested rutin in ocular tissues further substantiate its site-specific action.

摘要

目的

进行本研究以探索芦丁在预防威胁视力的糖尿病视网膜病变方面的潜力。

方法

将体重200 - 225克的Wistar白化大鼠(雌雄不限)腹腔注射45毫克/千克链脲佐菌素(pH 4.5)。血糖≥300毫克/分升的大鼠分为两组(每组n = 8)。第一组作为糖尿病对照组,口服生理盐水。第二组口服50毫克/千克芦丁,持续24周。在24周结束时,进行视网膜眼底和荧光素成像,处死大鼠,并进行视网膜生化评估。此外,在正常大鼠单次口服50毫克/千克剂量后评估芦丁的眼药代动力学。

结果

芦丁治疗显著(p < 0.001)降低了视网膜血管内皮生长因子、肿瘤坏死因子-α和醛糖还原酶。芦丁治疗显著(p < 0.001)提高了视网膜的总抗氧化能力水平。芦丁治疗组的眼底检查显示曲折指数显著降低,荧光素血管造影正常。在正常大鼠的视网膜和房水中检测到了芦丁。

结论

芦丁治疗显著阻止了糖尿病视网膜病变的生化紊乱。口服摄入的芦丁在眼组织中的分布进一步证实了其部位特异性作用。

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