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A novel approach of proteomics to study the mechanism of action of grape seed proanthocyanidin extracts on diabetic retinopathy in rats
作者单位:Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China 
基金项目:Acknowledgements: We are grateful to the personnel in Research Center for Proteome Analysis, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences and the Center for New Drug Evaluation of Shandong University. We are also grateful to Professor ZHANG Wei-dong and Professor ZHANG Cheng-mei for their assistance.
摘    要:Background Diabetic retinopathy (DR) is a leading cause of visual impairment and blindness among the people of occupational age. To prevent the progress of retina injury, effective therapies directed toward the key molecular target are required. Grape seed proanthocyanidin extracts (GSPE) have been reported to be effective in treating diabetic complications, while little is discussed about the functional protein changes. Methods We used streptozotocin (STZ) to induce diabetes in rats. GSPE (250 mg/kg body weight per day) were administrated to diabetic rats for 24 weeks. Serum glucose, glycated hemoglobin and advanced glycation end products (AGEs) were determined. Consequently, 2-D difference gel electrophoresis and mass spectrometry were used to investigate retina protein profiles among control, STZ-induced diabetic rats, and GSPE treated diabetic rats. Results GSPE significantly reduced the AGEs of diabetic rats (P 〈0.05). Moreover, GSPE significantly suppressed the vascular lesions of central regions, decreased capillary enlargements and neovascularization, similar to those of the control rats under light microscope. Eighteen proteins were found either up-regulated or down-regulated in the retina of STZ-induced diabetic rats. And seven proteins in the retina of diabetic rats were found to be back-regulated to normal levels after GSPE therapy. These back-regulated proteins are involved in many important biological processes such as heat shock, ubiquitin-proteasome system, cell proliferation, cell growth and glucose metabolism. Conclusions These findings might promote a better understanding for the mechanism of DR, and provide novel targets for evaluating the effects of GSPE therapy.

关 键 词:糖尿病  并发症  视网膜病变  葡萄籽提取物

A novel approach of proteomics to study the mechanism of action of grape seed proanthocyanidin extracts on diabetic retinopathy in rats
Authors:LI Man  MA Ya-bing  GAO Hai-qing  LI Bao-ying  CHENG Mei  XU Ling  LI Xiao-li  LI Xian-hua
Institution:LI Man(Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China);MA Ya-bing(Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China);GAO Hai-qing(Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China);LI Bao-ying(Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China);CHENG Mei(Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China);XU Ling(Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China);LI Xiao-li(Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China);LI Xian-hua(Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China);
Abstract:Background Diabetic retinopathy (DR) is a leading cause of visual impairment and blindness among the people of occupational age. To prevent the progress of retina injury, effective therapies directed toward the key molecular target are required. Grape seed proanthocyanidin extracts (GSPE) have been reported to be effective in treating diabetic complications, while little is discussed about the functional protein changes. Methods We used streptozotocin (STZ) to induce diabetes in rats. GSPE (250 mg/kg body weight per day) were administrated to diabetic rats for 24 weeks. Serum glucose, glycated hemoglobin and advanced glycation end products (AGEs) were determined. Consequently, 2-D difference gel electrophoresis and mass spectrometry were used to investigate retina protein profiles among control, STZ-induced diabetic rats, and GSPE treated diabetic rats. Results GSPE significantly reduced the AGEs of diabetic rats (P <0.05). Moreover, GSPE significantly suppressed the vascular lesions of central regions, decreased capillary enlargements and neovascularization, similar to those of the control rats under light microscope. Eighteen proteins were found either up-regulated or down-regulated in the retina of STZ-induced diabetic rats. And seven proteins in the retina of diabetic rats were found to be back-regulated to normal levels after GSPE therapy. These back-regulated proteins are involved in many important biological processes such as heat shock, ubiquitin-proteasome system, cell proliferation, cell growth and glucose metabolism. Conclusions These findings might promote a better understanding for the mechanism of DR, and provide novel targets for evaluating the effects of GSPE therapy.
Keywords:grape seed proanthocyanidin extracts  diabetic retinopathy  advanced glycation end products  proteomics
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