Abstract
ObjectivesDiabetic retinopathy (DR) is a common diabetic eye disease which is well-known as the result of microvascular retinal changes. Although the potential biological functions of astragaloside IV (AS IV) have long been described in traditional system of medicine, its protective effect on DR remains unclear. This study aims to investigate the function and mechanism of AS IV on type 2 diabetic db/db mice.MethodsDb/db mice were treated with AS IV (4.5 mg/kg or 9 mg/kg) or physiological saline by oral gavage for 20 weeks along with db/m mice. In each group, retinal ganglion cell (RGC) function was measured by pattern electroretinogram (ERG) and apoptosis was determined by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Blood and retina aldose reductase (AR) activity were quantified by chemiluminescence analysis. The expressions of phosporylated-ERK1/2, NF-κB were determined by Western blot analysis. Furthermore, the expression of related downstream proteins were quantified by Label-based Mouse Antibody Array.ResultsAdministration of AS IV significantly improved the amplitude in pattern ERG and reduced the apoptosis of RGCs.in db/db mice. Furthermore, downregulation of AR activity, ERK1/2 phosphorylation, NF-κB and related cytokine were observed in AS IV treatment group.ConclusionsOur study indicated that AS IV, as an inhibitor of AR, could prevent the activation of ERK1/2 phosporylation and NF-kB and further relieve the RGCs disfunction in db/db mice with DR. It has provided a basis for investigating the clinical efficacy of AR inhibitors in preventing DR.
Highlights
Diabetic retinopathy (DR) is known to be the most common microvascular complication of diabetes mellitus and is one of the most serious causes of visual impairment and blindness in developed countries [1,2,3]
Several vitro and vivo studies indicated that drugs with varying aldose reductase (AR) inhibiting efficacy show significant protection against diabetic complications, which provided evidences pointing to a significant role of AR in mediating hyperglycemic injury [19,20,21,22,23]
Status of Body Weight and Blood Glucose As can be seen from Fig 2A, mean weights of LC group were less than half of that in db/db mice groups from 8 weeks to 28 weeks
Summary
Diabetic retinopathy (DR) is known to be the most common microvascular complication of diabetes mellitus and is one of the most serious causes of visual impairment and blindness in developed countries [1,2,3]. Studies have shown this metabolic disorder can interfere with generation of neurotransmitters [8,9,10], inducing proapoptotic [11,12,13,14] and proinflammatory responses [15,16,17]. Accumulating evidence suggested that immunologic and inflammatory mechanisms play important roles in its development and progression [18]. Several vitro and vivo studies indicated that drugs with varying aldose reductase (AR) inhibiting efficacy show significant protection against diabetic complications, which provided evidences pointing to a significant role of AR in mediating hyperglycemic injury [19,20,21,22,23]
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