血管内皮细胞生长因子、谷氨酸、γ-氨基丁酸与增生性糖尿病视网膜病变的新生血管形成

The role of vascular endothelial growth factor,glutamate and γ-aminobutyric acid in neovascularization of proliferative diabetic retinopathy

目的 探讨血管内皮细胞生长因子 (vascularendothelialgrowthfactor,VEGF)、谷氨酸与γ 氨基丁酸 (γ aminobutyricacid ,GABA)在增生性糖尿病视网膜病变 (proliferativediabeticretinopathy ,PDR)新生血管形成中的作用。 方法 用定量双夹心酶联免疫吸附法检测 2 5例PDR患者 2 7只眼玻璃体VEGF含量 ,用高效液相色谱法检测其玻璃体氨基酸含量 ,并与 14例特发性黄斑裂孔患者 14只眼中玻璃体VEGF、谷氨酸和GABA的含量相比较。分析玻璃体VEGF含量与氨基酸含量的相关关系。 结果 PDR组患者玻璃体VEGF含量 (中位数 0 .41ng/ml ,四分位间距 0 .5 4ng/ml)显著高于对照组 (中位数 0 .0 17ng/ml,四分位间距0 .0 1ng/ml) (P <0 .0 0 1)。PDR组患者玻璃体谷氨酸含量 [(11.7± 3 .0 ) μmol/L]和GABA含量 [(7.2± 3 .9)μmol/L]亦显著高于对照组谷氨酸含量 [(5 .8± 0 .7) μmol/L]和GABA含量 [(3 .3± 2 .9) μmol/L] (P <0 .0 5 )。相关分析表明 ,谷氨酸、GABA均与VEGF含量有显著正相关关系。 结论 PDR患者玻璃体谷氨酸、GABA含量增高表明有视网膜缺血 ,它们与VEGF含量的正相关关系为视网膜缺血诱导新生血管产生提供了生物化学依据 ,也为PDR的治疗提供了新思路。

Purpose To investigate the roles of vascular endothelial growth factor (VEGF),glutamate and γ-aminobutyric acid (GABA) in neovascularization of proliferative diabetic retinopathy (PDR). Methods Vitreous samples were collected from 25 patients (27 eyes) with PDR and 14 patients (14 eyes) with idiopathic macular hole.VEGF levels were determined by ELISA.Amino acids analyses were performed by high-performance liquid chromatography. Results Patients with PDR had significantly higher concentrations of VEGF (median 0.41 ng/ml,quartile 0.54 ng/ml) than controls (median 0.017 ng/ml,quartile 0.01 ng/ml)(P<0.001).The levels of glutamate [(11.7±3.0) μmol/L] and GABA [(7.2±3.9)μmol/L)] were also higher in patients with PDR than glutamate [(5.8±0.7) μmol/L] and GABA [(3.3±2.9) μmol/L) in controls (P<0.05).The glutamate level and GABA level had a significantly positive correlation with VEGF level. Conclusions The increased levels of glutamate and GABA indicate retinal ischemia. The correlations of glutamate and GABA levels with an elevated VEGF level provide biochemical support for ischemia-induced neovascularization in patients with PDR.The findings present novel modalities in treatment of PDR.