Protective effects of astragaloside IV on db/db mice with diabetic retinopathy.

Protective effects of astragaloside IV on db/db mice with diabetic retinopathy.
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DOI:
10.1371/journal.pone.0112207
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Liu Q
Liu Q
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ding Y;Yuan S;Liu X;Mao P;Zhao C;Huang Q;Zhang R;Fang Y;Song Q;Yuan D;Xie P;Liu Y;Liu Q

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糖尿病视网膜病变(DR)是一种常见的糖尿病眼病,是视网膜微血管改变的结果。虽然黄芪甲苷(AS IV)的潜在生物学功能在传统医学体系中早已被描述,但其对DR的保护作用仍不清楚。本研究旨在探讨AS IV对2型糖尿病db/db小鼠的作用及其机制。给Db/db小鼠灌胃AS IV(4.5 mg/kg或9 mg/kg)或生理盐水,与db/m小鼠一起灌胃20周。各组大鼠视网膜神经节细胞(RGC)功能检测采用视网膜电图(ERG),细胞凋亡检测采用末端脱氧核苷酸转移酶dUTP缺口末端标记法(TUNEL)。用化学发光法测定血液和视网膜中的醛糖还原酶(AR)活性。Western印迹法检测磷酸化ERK1/2、NF-κB的表达。此外,相关下游蛋白的表达通过基于标记的小鼠抗体阵列进行定量。AS IV可显著提高db/db小鼠视网膜电图波幅,减少视网膜神经节细胞的凋亡率。此外,AS IV治疗组的AR活性、ERK1/2磷酸化、NF-κB及相关细胞因子表达下调。我们的研究表明,AS IV作为AR的抑制剂,可以阻止ERK1/2磷酸化和核因子-kB的激活,从而进一步缓解DR小鼠视网膜神经节细胞的功能障碍,为研究AR抑制剂预防DR的临床疗效提供了依据。
Diabetic 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. Db/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. Administration 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. Our 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.
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