2-SeCD對糖尿病視網(wǎng)膜微血管病變AGEs傳導通路的干預作用研究
發(fā)布時間：2018-08-11 10:30
【摘要】： 糖尿病視網(wǎng)膜病變(diabetic retinopathy, DR)為糖尿病嚴重微血管病變,已經(jīng)成為世界最重要致盲疾病之一。目前,對于糖尿病視網(wǎng)膜病變的發(fā)病機制和藥物的研究仍處于探索階段。糖基化終末產(chǎn)物(Advanced Glycation End products, AGEs)是已知的糖尿病微血管并發(fā)癥的發(fā)病機制之一,在糖尿病并發(fā)癥的發(fā)生、發(fā)展中起重要作用,其中確切的信號傳導通路,損傷基因表達等過程仍未徹底明了。因此更加深入的探討AGEs其可能的傳導通路,并在其可能的傳導通路上進行干預將有重要的意義。 本實驗針對糖尿病視網(wǎng)膜微血管病變發(fā)病機制中的AGEs途徑,利用免疫熒光染色、逆轉(zhuǎn)錄PCR、Western Blot等實驗發(fā)法及FFA等檢查手段,通過體內(nèi)和體外實驗研究AGEs對視網(wǎng)膜血管內(nèi)皮細胞、視網(wǎng)膜色素上皮細胞等作用的可能機制。并且應用由吉林大學超分子結(jié)構(gòu)與材料國家重點實驗室自行合成的谷胱甘肽過氧化物酶(GPX)模擬物：2-位硒橋聯(lián)環(huán)糊精(2-SeCD),對AGEs體內(nèi)及體外的作用進行干預和阻斷作用,以期達到對糖尿病視網(wǎng)膜疾病的預防和治療。 本研究的創(chuàng)新性包括：(1)2-SeCD為吉林大學超分子結(jié)構(gòu)與材料國家重點實驗室以CD為主體構(gòu)建的GPX模擬物,將2-SeCD應用于眼底疾病的干預國內(nèi)外未見報道；(2)本實驗動物模型的制作,采取尾靜脈注射AGEs的方法,FFA顯示造成了視網(wǎng)膜微血管的損傷及靜脈改變,模擬高血糖記憶效應。這種新型動物模型的成功建立國內(nèi)未見報道。
[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.
【學位授予單位】：吉林大學
【學位級別】：博士
【學位授予年份】：2010
【分類號】：R774.1
本文編號：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.
【學位授予單位】：吉林大學
【學位級別】：博士
【學位授予年份】：2010
【分類號】：R774.1
【參考文獻】
相關期刊論文 前3條
1 ;Advances in NF-κB Signaling Transduction and Transcription[J];Cellular & Molecular Immunology;2004年06期
2 楊前勇;鄒大進;;糖尿病中的氧化損傷與抗氧化研究進展[J];國際內(nèi)分泌代謝雜志;2006年S1期
3 趙琳;鄒大進;;氧化應激致胰島β細胞損傷的研究進展[J];國際內(nèi)分泌代謝雜志;2006年S1期
，本文編號：2176737
本文鏈接：http://sikaile.net/yixuelunwen/yank/2176737.html
最近更新
教材專著
