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研究白藜芦醇处理糖尿病大鼠眼组织后与眼新生血管相关的基因和氧化应激。

Investigation of ocular neovascularization-related genes and oxidative stress in diabetic rat eye tissues after resveratrol treatment.

机构信息

Department of Medical Biology and Genetics, Gazi University, Ankara, Turkey.

出版信息

J Med Food. 2012 Apr;15(4):391-8. doi: 10.1089/jmf.2011.0135. Epub 2011 Dec 22.

Abstract

Changes in vascular endothelial growth factor (VEGF), angiotensin-converting enzyme (ACE), matrix metalloproteinase (MMP)-9, and endothelial nitric oxide synthase (eNOS) mRNA expression profiles and oxidative stress in the eye tissue microenviroment may have important roles in ocular neovascularization and permeability in proliferative diabetic retinopathy. The present study investigated the effects of resveratrol (RSV) treatment on the mRNA expression profile of VEGF, ACE, MMP-9, and eNOS, which are associated with vascular neovascularization, and glutathione, protein carbonyl, and nitrite-nitrate levels, which are markers of oxidative stress in eyes of diabetic rats. Twenty-four Wistar albino male rats were divided into four groups. After diabetes induction with streptozotocin (10 mg/kg/day) RSV was administered to the RSV and diabetes mellitus (DM) + RSV groups for 4 weeks. The mRNA levels were measured by quantitative real-time polymerase chain reaction assay, and biochemical estimations were determined with spectrophotometric assays in eye homogenates. The mRNA expression levels of VEGF, ACE, and MMP-9 were increased in the DM group compared with the control group, and RSV treatment decreased their mRNA levels. Expression of eNOS mRNA was increased in the RSV and DM groups and decreased in the DM + RSV group. Nitrite-nitrate levels and protein carbonyl content were increased and glutathione levels were decreased in the DM group compared with controls. Consequently, these data suggest that RSV suppressed the expression of eNOS, which is actively involved in the inflammation and healing process in chronic diabetes. Although oxidative stress was increased in eye tissue from diabetic rats, mRNA levels of VEGF, MMP-9, and ACE genes associated with vascular remodeling did not change in diabetic eyes.

摘要

血管内皮生长因子 (VEGF)、血管紧张素转换酶 (ACE)、基质金属蛋白酶 (MMP)-9 和内皮型一氧化氮合酶 (eNOS)mRNA 表达谱的变化以及眼组织微环境中的氧化应激可能在增生性糖尿病视网膜病变的眼新生血管形成和通透性中起重要作用。本研究探讨了白藜芦醇 (RSV) 治疗对与血管新生相关的 VEGF、ACE、MMP-9 和 eNOSmRNA 表达谱以及与糖尿病大鼠眼氧化应激相关的谷胱甘肽、蛋白羰基和亚硝酸盐-硝酸盐水平的影响。将 24 只 Wistar 白化雄性大鼠分为四组。用链脲佐菌素 (10mg/kg/天) 诱导糖尿病后,RSV 被给予 RSV 和糖尿病 (DM) + RSV 组 4 周。通过定量实时聚合酶链反应测定法测量 mRNA 水平,并通过分光光度法在眼匀浆中测定生化估计值。与对照组相比,DM 组的 VEGF、ACE 和 MMP-9mRNA 表达水平升高,RSV 治疗降低了其 mRNA 水平。RSV 和 DM 组的 eNOSmRNA 表达增加,DM + RSV 组减少。与对照组相比,DM 组的硝酸盐-硝酸盐水平和蛋白羰基含量增加,谷胱甘肽水平降低。因此,这些数据表明 RSV 抑制了 eNOS 的表达,eNOS 积极参与慢性糖尿病中的炎症和愈合过程。尽管糖尿病大鼠眼组织中的氧化应激增加,但与血管重塑相关的 VEGF、MMP-9 和 ACE 基因的 mRNA 水平在糖尿病眼中没有改变。

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