Plasma metabolic profile reveals PGF2α protecting against non-proliferative diabetic retinopathy in patients with type 2 diabetes
Plasma metabolic profile reveals PGF2α protecting against non-proliferative diabetic retinopathy in patients with type 2 diabetes
复制标题
血浆代谢谱显示 PGF2α 可以预防 2 型糖尿病患者发生非增殖性糖尿病视网膜病变。
DOI：
10.1016/j.bbrc.2018.01.188
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发表时间：
2018-02-19
影响因子：
3.1
通讯作者：
Ai, Ding
中科院分区：
文献类型：
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作者：
Peng, Liyuan;Sun, Bei;Ai, Ding
糖尿病视网膜病变（DR）是糖尿病最常见的微血管并发症，也是全球成人失明的主要原因。非增殖性DR（NPDR）是DR的第一阶段，但目前很少推荐干预。类花生酸在维持血管内环境稳定中起重要作用。然而，类二十烷酸在NPDR中的功能仍然未知。在这项研究中，我们研究了2型糖尿病与NPDR之间血浆中类花生酸谱的差异。选择50例2型糖尿病患者，根据眼底照片分为非DR（non-DR，NDR）组和NPDR组。采用LC-MS/MS法测定血浆中类花生酸的浓度，采用粘附法和transwell法分别检测代谢产物对原代牛视网膜周细胞（BRPC）的粘附和迁移作用。采用链霉素（STZ）诱导的糖尿病小鼠模型，通过视网膜免疫荧光染色和荧光共聚焦显微镜检查，检测所选代谢产物的保护作用。前列腺素2 α（PGF 2 α）在NPDR组较NDR组显著降低，且与NPDR呈负相关。在体外，发现PGF 2 α通过激活前列腺素F受体（FP受体）和随后增加原代牛视网膜周细胞中RhoA活性来加速粘附和迁移。在STZ诱导的糖尿病小鼠模型中，给予PGF 2 α类似物可减轻视网膜毛细血管的损伤。我们的研究结果表明，PGF 2 α可能是T2 D患者NPDR进展的保护因素。PGF 2 α的保护机制是通过FP受体/RhoA通路增加周细胞运动性。(C)2018爱思唯尔公司All rights reserved.
Diabetic retinopathy (DR) is the most frequent microvascular complications of diabetes and the leading cause of blindness in adults worldwide. Non-proliferative DR (NPDR) is the first stage of DR but currently has few recommended intervention. Eicosanoids play important roles in maintaining vessel homeostasis. However, the functions of eicosanoids in NPDR are still unknown. In this study, we investigated the eicosanoids profile difference in plasma between type 2 diabetes with NPDR or not. A total of 50 patients with type 2 diabetes were recruited and divided into non-DR (NDR) group and NPDR group based on fundus photographs. The eicosanoids profiles in plasma were determined by LC-MS/MS. Adhesion and transwell assay were used to detect the adhesion and migration effects of metabolites on primary bovine retinal pericyte cells (BRPC), respectively. Streptomycin (STZ)-induced diabetic mouse model was used to test the protective effects of selected metabolites according to retinal immunofluorescence staining and fluorescence confocal microscopy. Prostaglandin 2 alpha (PGF2 alpha) was decreased significantly in NPDR group compared to NDR group and negatively correlated with NPDR. In vitro, PGF2 alpha was found to accelerate adhesion and migration by activating prostaglandin F receptor (FP receptor) and subsequent increasing RhoA activity in primary bovine retinal pericyte. Administration of PGF2 alpha analogue diminished the damage on retinal capillary in an STZ-induced diabetic mouse model. Our results suggested that PGF2 alpha may be a protective factor in the progression of NPDR in T2D patients. The protective mechanism of PGF2 alpha was to increase pericyte mobility through FP receptor/RhoA pathway. (C) 2018 Elsevier Inc. All rights reserved.