维生素 B 补充对糖尿病大鼠视网膜病变的影响。
Effect of vitamin B supplementation on retinal lesions in diabetic rats.
机构信息
Biochemistry Division, National Institute of Nutrition, Hyderabad, India.
出版信息
Mol Vis. 2020 Apr 24;26:311-325. eCollection 2020.
PURPOSE
Diabetic retinopathy (DR) is the most common complication of diabetes involving microvasculature and neuronal alterations in the retina. Previously, we reported that vitamin B deficiency could be an independent risk factor for DR in humans. However, the effect of vitamin B supplementation in experimental DR is unknown. Thus, in this study, we investigated the impact of dietary supplementation of vitamin B on retinal changes in diabetic rats.
METHODS
Diabetes was induced in 2-month-old Sprague-Dawley rats and maintained for 4 months. One group of diabetic rats were fed normal levels of vitamin B, and one group double the quantity of vitamin B (50 µg/kg diet). Vitamin B and homocysteine levels in the plasma were analyzed with radioimmunoassay (RIA) and high-performance liquid chromatography (HPLC), respectively. At the end of 4 months of experimentation, the eyeballs were collected. Retinal changes were analyzed with hematoxylin and eosin (H&E) staining, immunoblotting, and immunofluorescence methods.
RESULTS
Dietary supplementation of vitamin B had no effect on food intake, bodyweight, fasting blood glucose, and plasma homocysteine levels in the diabetic rats. However, vitamin B supplementation prevented loss of rhodopsin, and overexpression of VEGF, and completely prevented overexpression of HIF1α, GFAP, and endoplasmic reticulum (ER) stress markers (GRP78, ATF6α, XBP1, CHOP, and caspase 12) in the diabetic rat retina. Further, vitamin B ameliorated apoptosis in the retina as shown with terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and prevented retinal thinning.
CONCLUSIONS
Vitamin B supplementation of diabetic rats appeared to be beneficial by circumventing retinal hypoxia, VEGF overexpression, and ER stress-mediated cell death in the retina. The present study adds another potential therapeutic strategy of vitamin B in diabetes.
目的
糖尿病视网膜病变（DR）是糖尿病最常见的并发症，涉及视网膜微血管和神经元改变。此前，我们报道维生素 B 缺乏可能是人类 DR 的一个独立危险因素。然而，维生素 B 补充剂对实验性 DR 的影响尚不清楚。因此，在这项研究中，我们研究了饮食补充维生素 B 对糖尿病大鼠视网膜变化的影响。
方法
将 2 月龄 Sprague-Dawley 大鼠诱导糖尿病，并维持 4 个月。一组糖尿病大鼠给予正常水平的维生素 B，一组给予维生素 B 双倍量（50µg/kg 饮食）。采用放射免疫分析（RIA）和高效液相色谱（HPLC）分别分析血浆中维生素 B 和同型半胱氨酸水平。在实验结束 4 个月时，收集眼球。采用苏木精和伊红（H&E）染色、免疫印迹和免疫荧光方法分析视网膜变化。
结果
饮食补充维生素 B 对糖尿病大鼠的食物摄入量、体重、空腹血糖和血浆同型半胱氨酸水平没有影响。然而，维生素 B 补充剂可防止视紫红质丢失和 VEGF 过表达，并完全防止 HIF1α、GFAP 和内质网（ER）应激标志物（GRP78、ATF6α、XBP1、CHOP 和 caspase 12）在糖尿病大鼠视网膜中的过表达。此外，维生素 B 通过末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）改善视网膜细胞凋亡，并防止视网膜变薄。
结论
糖尿病大鼠补充维生素 B 似乎通过避免视网膜缺氧、VEGF 过表达和 ER 应激介导的细胞死亡而有益。本研究为维生素 B 在糖尿病中的另一种潜在治疗策略增添了证据。
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