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光照减少通过抗炎作用和增加视网膜胆固醇周转率减轻链脲佐菌素诱导的糖尿病视网膜血管变化和神经胶质增生。

Reduced light exposure mitigates streptozotocin-induced vascular changes and gliosis in diabetic retina by an anti-inflammatory effect and increased retinal cholesterol turnover.

机构信息

Eye Hospital, University Clinical Centre of Serbia, 11000, Belgrade, Serbia.

Department of Molecular Biology and Endocrinology, Vinca - Institute for Nuclear Sciences, National Institute of Republic of Serbia, University of Belgrade, 11000, Belgrade, Serbia.

出版信息

Chem Biol Interact. 2024 May 1;394:110996. doi: 10.1016/j.cbi.2024.110996. Epub 2024 Apr 7.

Abstract

Diabetic retinopathy is not cured efficiently and changes of lifestyle measures may delay early retinal injury in diabetes. The aim of our study was to investigate the effects of reduced daily light exposure on retinal vascular changes in streptozotocin (STZ)-induced model of DM with emphasis on inflammation, Aqp4 expression, visual cycle and cholesterol metabolism-related gene expression in rat retina and RPE. Male Wistar rats were divided into the following groups: 1. control; 2. diabetic group (DM) treated with streptozotocin (100 mg/kg); 3. group exposed to light/dark cycle 6/18 h (6/18); 4. diabetic group exposed to light/dark cycle 6/18 h (DM+6/18). Retinal vascular abnormalities were estimated based on lectin staining, while the expression of genes involved in the visual cycle, cholesterol metabolism, and inflammation was determined by qRT-PCR. Reduced light exposure alleviated vasculopathy, gliosis and the expression of IL-1 and TNF-α in the retina with increased perivascular Aqp4 expression. The expression of genes involved in visual cycle and cholesterol metabolism was significantly up-regulated in RPE in DM+6/18 vs. DM group. In the retina only the expression of APOE was significantly higher in DM+6/18 vs. DM group. Reduced light exposure mitigates vascular changes and gliosis in DM via its anti-inflammatory effect, increased retinal cholesterol turnover and perivascular Aqp4 expression.

摘要

糖尿病性视网膜病变的治疗效果并不理想,而生活方式的改变可能会延缓糖尿病早期的视网膜损伤。本研究旨在探讨减少每日光照暴露对链脲佐菌素(STZ)诱导的糖尿病模型大鼠视网膜血管变化的影响,重点研究炎症、Aqp4 表达、视觉循环以及胆固醇代谢相关基因在大鼠视网膜和 RPE 中的表达变化。雄性 Wistar 大鼠分为以下几组:1. 对照组;2. 糖尿病组(DM)用链脲佐菌素(100mg/kg)处理;3. 6/18 光照/黑暗循环组(6/18);4. 糖尿病 6/18 光照/黑暗循环组(DM+6/18)。通过凝集素染色评估视网膜血管异常,通过 qRT-PCR 确定参与视觉循环、胆固醇代谢和炎症的基因表达。减少光照暴露可减轻血管病变、神经胶质增生以及视网膜中 IL-1 和 TNF-α 的表达,并增加血管周围 Aqp4 的表达。与 DM 组相比,DM+6/18 组 RPE 中与视觉循环和胆固醇代谢相关的基因表达显著上调。仅在 DM+6/18 组与 DM 组相比,视网膜中 APOE 的表达显著升高。减少光照暴露通过其抗炎作用、增加视网膜胆固醇周转率和血管周围 Aqp4 的表达来减轻 DM 中的血管变化和神经胶质增生。

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