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槲皮素对糖尿病视网膜病变大鼠MCP-1、MMP-9和VEGF表达的影响

Effects of quercetin on the expression of MCP-1, MMP-9 and VEGF in rats with diabetic retinopathy.

作者信息

Chen Bin, He Tao, Xing Yiqiao, Cao Ting

机构信息

Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.

出版信息

Exp Ther Med. 2017 Dec;14(6):6022-6026. doi: 10.3892/etm.2017.5275. Epub 2017 Oct 10.

DOI:10.3892/etm.2017.5275
PMID:29285153
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5740807/
Abstract

Diabetic retinopathy, a severe complication of diabetes, is the leading cause of blindness in the developed world. This study investigated the effects of quercetin on levels of monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in serum of rats with diabetic retinopathy, and explored the functional mechanisms of quercetin in the treatment of diabetic retinopathy. Twenty rats with induced diabetes were divided into a model group and a quercetin group, with 10 rats in each group. Ten healthy rats were also included to serve as a control group. Rats in the quercetin group were treated with an intragastric injection of quercetin (150 mg/kg), while the same amount of sodium carboxymethyl cellulose (CMCNa) was used for rats in the model group and the control group. The treatment was performed once per day and blood glucose was measured in each group at 0, 10 and 20 weeks after the first treatment. Blood glucose tests showed that quercetin did not reduce blood glucose in rats with diabetes. However, pathological examination showed that quercetin could relieve pathological changes caused by diabetes, such as retinal edema and vacuoles. ELISA results showed that, compared with the control group, levels of MCP-1, MMP-9 and VEGF in the model group were significantly increased (P<0.01). No significant difference in serum MCP-1 content was found between the model group and the quercetin group, but levels of MMP-9 and VEGF were significantly decreased in the quercetin group (P<0.01). Results of RT-PCR and western blot analysis showed that, compared with the control group, levels of MCP-1, MMP-9 and VEGF mRNA and protein in the retinal tissue of rats in the model group were significantly increased (P<0.01). No significant differences in expression levels of MCP-1 mRNA and protein were found between the model group and the quercetin group, but levels of MMP-9 and VEGF mRNA and protein were significantly decreased in the quercetin group (P<0.01). Quercetin has a certain therapeutic effect on rats with diabetic retinopathy and its effect may be achieved by reducing the expression of MMP-9 and VEGF, but not the inflammatory mediator, MCP-1.

摘要

糖尿病性视网膜病变是糖尿病的一种严重并发症,是发达国家失明的主要原因。本研究探讨了槲皮素对糖尿病性视网膜病变大鼠血清中单核细胞趋化蛋白-1(MCP-1)、基质金属蛋白酶-9(MMP-9)和血管内皮生长因子(VEGF)水平的影响,并探讨了槲皮素治疗糖尿病性视网膜病变的作用机制。将20只诱导糖尿病大鼠分为模型组和槲皮素组,每组10只。另选取10只健康大鼠作为对照组。槲皮素组大鼠经胃内注射槲皮素(150mg/kg),模型组和对照组大鼠则注射等量的羧甲基纤维素钠(CMCNa)。每天给药1次,在首次给药后0、10和20周测量每组大鼠的血糖。血糖检测结果显示,槲皮素不能降低糖尿病大鼠的血糖。然而,病理检查表明,槲皮素可以缓解糖尿病引起的病理变化,如视网膜水肿和空泡形成。酶联免疫吸附测定(ELISA)结果显示,与对照组相比,模型组中MCP-1、MMP-9和VEGF的水平显著升高(P<0.01)。模型组与槲皮素组血清MCP-1含量无显著差异,但槲皮素组MMP-9和VEGF水平显著降低(P<0.01)。逆转录聚合酶链反应(RT-PCR)和蛋白质免疫印迹分析结果显示,与对照组相比,模型组大鼠视网膜组织中MCP-1、MMP-9和VEGF的mRNA和蛋白水平显著升高(P<0.01)。模型组与槲皮素组MCP-1的mRNA和蛋白表达水平无显著差异,但槲皮素组MMP-9和VEGF的mRNA和蛋白水平显著降低(P<0.01)。槲皮素对糖尿病性视网膜病变大鼠具有一定的治疗作用,其作用可能是通过降低MMP-9和VEGF的表达来实现的,而不是通过降低炎症介质MCP-1来实现的。

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