Physiology Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
J Physiol Biochem. 2021 May;77(2):305-320. doi: 10.1007/s13105-021-00799-9. Epub 2021 Feb 26.
Diabetic retinopathy (DR) is the most common diabetic neurovascular complication, and the leading cause of preventable blindness among working-age individuals. Recently, agmatine, the endogenous decarboxylated L-arginine, has gained attention as a pleiotropic agent that modulates the diabetes-associated decline in quality of life, and exhibited varied protective biological effects. Diabetes was induced by a single streptozotocin (STZ, 50 mg/kg, i.p.) injection. When diabetes was verified, the animals were randomly allocated into three groups (16 rat each); diabetic, agmatine-treated diabetic (1 mg/kg, daily, for 12 weeks), and control group. Blood glucose homeostasis, retinal redox status, apoptotic parameters, nitric oxide synthase (NOS), nitric oxide (NO), vascular endothelial growth factor (VEGF), glutamate, glutamine, glutamine synthase (GS) activity, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), and mitogen-activated protein kinase (MAPKs) pathways were assayed biochemically. Retinal vascular permeability was measured. Retinal morphology was evaluated by hematoxylin and eosin staining. Retinal N-methyl-D-aspartic acid receptor1 (NMDAR1) and glutamate aspartate transporter (GLAST) mRNA were quantified. Glucose transporter 1, pro-caspase3, and glial fibrillary acidic protein (GFAP) expression were quantified by immunohistochemistry. Chronic agmatine treatment abrogated STZ-induced retinal neurodegeneration features including gliosis, and neuronal apoptosis, restored retinal vascular permeability, mostly through antioxidant, anti-apoptotic capacity, abolishing glutamate excitotoxicity, modulating the activity of NMDARs, MAPKs/NFκB, and NOS/NO pathways. By restoring the molecular and functional background of retinal neurovascular homeostatic balance, agmatine would be appropriate therapeutic option acting upstream of the DR, impeding its progression.
糖尿病性视网膜病变（DR）是最常见的糖尿病性神经血管并发症，也是工作年龄人群中可预防失明的主要原因。最近，胍丁胺作为一种内源性精氨酸脱羧产物，作为一种多效调节剂引起了人们的关注，它可以调节与糖尿病相关的生活质量下降，并表现出多种保护的生物学作用。通过单次链脲佐菌素（STZ，50mg/kg，腹腔注射）注射诱导糖尿病。当糖尿病得到验证时，将动物随机分为三组（每组 16 只大鼠）；糖尿病组、胍丁胺治疗糖尿病组（1mg/kg，每天，持续 12 周）和对照组。通过生化方法测定血糖稳态、视网膜氧化还原状态、凋亡参数、一氧化氮合酶（NOS）、一氧化氮（NO）、血管内皮生长因子（VEGF）、谷氨酸、谷氨酰胺、谷氨酰胺合成酶（GS）活性、核因子κ轻链增强子的 B 细胞（NFκB）和丝裂原活化蛋白激酶（MAPKs）途径。测量视网膜血管通透性。通过苏木精和伊红染色评估视网膜形态。定量测定视网膜 N-甲基-D-天冬氨酸受体 1（NMDAR1）和谷氨酸天冬氨酸转运体（GLAST）mRNA。通过免疫组织化学定量测定葡萄糖转运蛋白 1、原半胱天冬酶 3 和神经胶质纤维酸性蛋白（GFAP）的表达。慢性胍丁胺治疗可消除 STZ 诱导的视网膜神经退行性变特征，包括神经胶质增生和神经元凋亡，恢复视网膜血管通透性，主要通过抗氧化、抗凋亡作用，消除谷氨酸兴奋性毒性，调节 NMDARs、MAPKs/NFκB 和 NOS/NO 途径的活性。通过恢复视网膜神经血管内稳态的分子和功能背景，胍丁胺可能是一种适当的治疗选择，作用于 DR 的上游，阻止其进展。
