2-SeCD对糖尿病视网膜微血管病变AGEs传导通路的干预作用研究
发布时间：2018-08-11 10:30
【摘要】： 糖尿病视网膜病变(diabetic retinopathy, DR)为糖尿病严重微血管病变,已经成为世界最重要致盲疾病之一。目前,对于糖尿病视网膜病变的发病机制和药物的研究仍处于探索阶段。糖基化终末产物(Advanced Glycation End products, AGEs)是已知的糖尿病微血管并发症的发病机制之一,在糖尿病并发症的发生、发展中起重要作用,其中确切的信号传导通路,损伤基因表达等过程仍未彻底明了。因此更加深入的探讨AGEs其可能的传导通路,并在其可能的传导通路上进行干预将有重要的意义。 本实验针对糖尿病视网膜微血管病变发病机制中的AGEs途径,利用免疫荧光染色、逆转录PCR、Western Blot等实验发法及FFA等检查手段,通过体内和体外实验研究AGEs对视网膜血管内皮细胞、视网膜色素上皮细胞等作用的可能机制。并且应用由吉林大学超分子结构与材料国家重点实验室自行合成的谷胱甘肽过氧化物酶(GPX)模拟物：2-位硒桥联环糊精(2-SeCD),对AGEs体内及体外的作用进行干预和阻断作用,以期达到对糖尿病视网膜疾病的预防和治疗。 本研究的创新性包括：(1)2-SeCD为吉林大学超分子结构与材料国家重点实验室以CD为主体构建的GPX模拟物,将2-SeCD应用于眼底疾病的干预国内外未见报道；(2)本实验动物模型的制作,采取尾静脉注射AGEs的方法,FFA显示造成了视网膜微血管的损伤及静脉改变,模拟高血糖记忆效应。这种新型动物模型的成功建立国内未见报道。
[Abstract]:Diabetic retinopathy (diabetic retinopathy, DR) is a severe diabetic microvascular disease and has become one of the most important blinding diseases in the world. At present, the pathogenesis of diabetic retinopathy and drug research is still in the exploratory stage. Glycation end product (Advanced Glycation End products, AGEs) is one of the known pathogenesis of diabetic microvascular complications, which plays an important role in the occurrence and development of diabetic complications, in which the exact signal transduction pathway. The process of damage gene expression is still unclear. Therefore, it is of great significance to probe into the possible conduction pathway of AGEs and to intervene in its possible conduction pathway. In this study, the AGEs pathway in the pathogenesis of diabetic retinopathy was studied by means of immunofluorescence staining, reverse transcriptase polymerase chain reaction (RT-PCR), Western Blot and FFA in vitro and in vivo to study the effect of AGEs on retinal vascular endothelial cells (RVEC). The role of retinal pigment epithelial cells and other possible mechanisms. In addition, glutathione peroxidase (GPX) mimetic of glutathione peroxidase (GPX) was synthesized by the State key Laboratory of Supermolecular structure and Materials of Jilin University. 2-SeCD was bridged with selenium at the 2 position of AGEs. The effects of AGEs in vivo and in vitro were interfered and blocked. In order to achieve the prevention and treatment of diabetic retinopathy. The innovations of this study include: (1) 2-SeCD is a GPX simulator constructed by CD in the State key Laboratory of Supramolecular structure and Materials of Jilin University. The intervention of 2-SeCD in ocular fundus diseases has not been reported at home and abroad; (2) the establishment of animal model of this experiment. AGEs was injected into caudal vein to show the damage of retinal microvessel and the change of vein, which simulated hyperglycemia memory effect. The successful establishment of this new animal model has not been reported in China.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2010
【分类号】：R774.1
本文编号：2176737
[Abstract]:Diabetic retinopathy (diabetic retinopathy, DR) is a severe diabetic microvascular disease and has become one of the most important blinding diseases in the world. At present, the pathogenesis of diabetic retinopathy and drug research is still in the exploratory stage. Glycation end product (Advanced Glycation End products, AGEs) is one of the known pathogenesis of diabetic microvascular complications, which plays an important role in the occurrence and development of diabetic complications, in which the exact signal transduction pathway. The process of damage gene expression is still unclear. Therefore, it is of great significance to probe into the possible conduction pathway of AGEs and to intervene in its possible conduction pathway. In this study, the AGEs pathway in the pathogenesis of diabetic retinopathy was studied by means of immunofluorescence staining, reverse transcriptase polymerase chain reaction (RT-PCR), Western Blot and FFA in vitro and in vivo to study the effect of AGEs on retinal vascular endothelial cells (RVEC). The role of retinal pigment epithelial cells and other possible mechanisms. In addition, glutathione peroxidase (GPX) mimetic of glutathione peroxidase (GPX) was synthesized by the State key Laboratory of Supermolecular structure and Materials of Jilin University. 2-SeCD was bridged with selenium at the 2 position of AGEs. The effects of AGEs in vivo and in vitro were interfered and blocked. In order to achieve the prevention and treatment of diabetic retinopathy. The innovations of this study include: (1) 2-SeCD is a GPX simulator constructed by CD in the State key Laboratory of Supramolecular structure and Materials of Jilin University. The intervention of 2-SeCD in ocular fundus diseases has not been reported at home and abroad; (2) the establishment of animal model of this experiment. AGEs was injected into caudal vein to show the damage of retinal microvessel and the change of vein, which simulated hyperglycemia memory effect. The successful establishment of this new animal model has not been reported in China.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2010
【分类号】：R774.1
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2 杨前勇;邹大进;;糖尿病中的氧化损伤与抗氧化研究进展[J];国际内分泌代谢杂志;2006年S1期
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