脂质对糖尿病视网膜TGF-β2与TβRⅡ表达及内皮细胞凋亡的影响
|
摘要
研究背景
糖尿病视网膜病变(Diabetic Retinopathy,DR)是患者致盲的主要原因之一,其确切的发病机制尚不清楚,目前认为是多种因素协同作用的结果。在过去的几十年来对这种高葡萄糖导致的疾病的认识有很大的进展,但脂代谢紊乱在糖尿病微血管病变中的作用机制目前尚不清楚。临床观察表明脂代谢紊乱与糖尿病视网膜病变有密切关系,因此研究其作用机制就显得尤为重要。
DR的病理改变包括毛细血管闭塞,微动脉瘤形成,血管壁内周细胞的选择性丧失,基底膜的增厚和新生血管形成。在DR中,视网膜微血管内皮细胞、Muller细胞、神经节细胞、周细胞通过凋亡而丧失,这种情况在DR的早期就可出现,目前国内外还未见有关脂代谢紊乱与视网膜内皮细胞凋亡关系的相关报道。
新生血管形成与视网膜缺血关系密切,生长因子在其病理过程中起重要作用。缺血的视网膜能分泌生长因子,刺激残存的血管增殖。脂代谢紊乱导致DR的分子机制目前仍不清楚。TGF-β与内皮细胞的增殖、黏附和细胞外基质的聚积有关。在哺乳动物中,TGF-β有三种异构体,命名为TGF-β1、TGF-β2、TGF-γ3。TGF-β在眼组织中有广泛表达,其中在视网膜组织中主要表达TGF-β2。TGF-β作为一种具有双相功能的生长调节子,其刺激或抑制增殖的作用依赖细胞的培养条件、TGF-β的浓度及其他协同调节的细胞因子。TGF-β通过调节内皮细胞的增殖、移行,促进血管腔的形成和成熟而参与新生血管形成。
TGF-β通过与靶细胞表面的特异受体结合而发挥生物效应。细胞有表面的二种TGF-β受体(TβRⅠ、TβRⅡ),这二种受体的跨膜丝氨酸/苏氨酸部分通过形成受体复合物参与TGF-β的信号通路,从而调节TGF-β的效应,Ⅱ型受体的激酶活性是信号传导所必需的。目前还未见有关脂代谢紊乱对视网膜TGF-β2及其Ⅱ型受体影响的相关报道。
基于上述原因,本研究探讨脂毒性对视网膜TGF-β2、TβRⅡ表达及内皮细胞凋亡的影响。
第一章:高脂喂养对糖尿病大鼠视网膜TGF-β2与TβRⅡmRNA表达的影响
目的:探讨高脂喂养的糖尿病大鼠视网膜中TGF-β2及TβRⅡmRNA的表达。方法:应用RT-PCR方法检测高脂喂养的糖尿病大鼠视网膜中TGF-β2及TβRⅡmRNA的表达水平。结果:糖尿病大鼠视网膜中TGF-β2 mRNA的表达高于非糖尿病大鼠视网膜(P＜0.01);高脂喂养的糖尿病大鼠视网膜中TGF-β2 mRNA的表达高于普通喂养的糖尿病大鼠视网膜(P＜0.01);TβRⅡmRNA的表达水平在非糖尿病大鼠视网膜与糖尿病大鼠视网膜间比较无明显差异;高脂喂养的糖尿病大鼠视网膜中TβRⅡmRNA的表达水平与普通喂养的糖尿病大鼠间比较亦无明显差异。结论:高脂喂养的糖尿病大鼠视网膜中TGF-β2 mRNA的表达水平升高。高脂喂养对糖尿病大鼠视网膜中TβRⅡmRNA的表达无影响。
第二章溶血卵磷脂对牛视网膜微血管内皮细胞凋亡的影响
目的:探讨溶血卵磷脂(LPC)对牛视网膜微血管内皮细胞(BRECs)凋亡的影响。方法:视网膜微血管消化分离后,采用含20%胎牛血清、5%PPP和20μl/ml视网膜浸出液的DMEM培养基,结合原代细胞的分离、除杂培养BRECs。培养的BRECs中加入不同浓度的LPC(0～60umol/L),分别培养6小时、12小时、24小时,通过吖啶橙染色在荧光显微镜下观察细胞凋亡,流式细胞检测细胞凋亡率,F2000荧光分光光度计测细胞内钙离子浓度并计算游离钙浓度。结果:(1)含20%FBS的DMEM培养基中加入5%PPP及20μl/ml的视网膜浸出液,结合原代细胞克隆的分离、除杂,可获得较纯净的BRECs;(2)LPC浓度为60 umol/L作用BRECs 24小时后,BRECs凋亡率明显高于LPC浓度为20umol/L及40umol/L时;LPC浓度从20umol/L增加到60umol/L过程中,细胞内游离钙离子浓度明显增加,而且细胞内游离钙离子浓度的增加与LPC的作用时间有关,作用时间越长,钙离子浓度越高。结论:(1)通过选择性培养能获得高纯度的BRECs,并能连续传代;(2)LPC能增加细胞内游离钙离子浓度,促使BREC的凋亡,而且LPC的这种作用具有时间和剂量依赖性。
第三章:LPC对牛视网膜微血管内皮细胞TGF-β2与TβRⅡmRNA表达的影响
目的:探讨不同浓度的LPC对牛视网膜微血管内皮细胞TGF-β2与TβRⅡmRNA表达的影响。方法:原代分离、培养牛的视网膜微血管内皮细胞,加入不同浓度的LPC(0～60umol/L),分别培养6小时、12小时、24小时,RT-PCR检测TGF-β_2 mRNA表达水平,半巢式RT-PCR检测TβRⅡmRNA的表达水平。结果:RT-PCR结果表明,LPC浓度为40umol/L作用12小时后,TGF-β2 mRNA水平明显高于LPC浓度为20 umol/L和60umol/L;LPC浓度改变对TβRⅡmRNA的表达无明显影响。结论:LPC能调节牛视网膜内皮细胞TGF-β2的表达;LPC对牛视网膜内皮细胞TβRⅡ的表达无明显影响;
Research background
Diabetic retinopathy is one of the important cause of visual disability in diabetic subjects,its precisely mechanism is not yet fully understood, and recognized as the result of multiple factors synergistic action.Despite considerable progress in understanding of hyperglycemia-induced disease over the past decade,the link between lipid metabolic disorders and retinopathy still eludes us.Clinical observations have shown that there is a intimate link between lipid metabolic disorders and retinopathy,so it is important to investigate the mechanism by which lipid leads to diabetic retinopathy.
Diabetic retinopathy is characterized by capillary occlusions, microaneurysms,selective loss of intramural pericytes,acellular capillaries,thickening of the basement membrane,and finally, angiogenesis and neovascularization.In the pathogenesis of retinopathy in diabetes,retinal microvascular endothelial,Muller cell,and ganglion cells and pericytes are lost selectively via apoptosis before other histopathology is detectable.It is not reported Whether dyslipidemia can induce the apoptosis of retinal endothelial cells.
Neovascularization is strongly associated with retinal ischaemia, and growth factors have been implicated in its pathogenesis.The ischaemic retina is assumed to secrete growth factors which stimulate residual vessels to proliferate.The molecular mechanisms of dyslipidemia leading to diabetic retinopathy have not been studied in detail.Transforming growth factor beta(TGF-β) is involved in endothelial cell proliferation,adhesion,and deposition extracellular maxtrix.There has three well-defined mammalian isoforms,numerically designated as TGF-β1-3,eye tissue extensively expresses TGF-β, principally TGF-β2 in retina tissue.TGF-βacts as a bifunctional regulator of growth and it may either stimulate or inhibit proliferation depending on cell culture condition,TGF-βconcentration,or other cytokine.TGF-βis able to regulate angiogenesis by the regulation of endothelial cell growth and migration and the promotion of tube formation and vessel maturation.
TGF-βexerts its biological effects by binding to specific cell surface receptors on target cells.Two cell surface TGF-βreceptor(TβRⅠ,TβRⅡ) proteins regulate the effects of TGF-βand the complex consisting of the typeⅠand typeⅡtransmembrane serine / threonine participates in signaling pathway and kinase activity of the typeⅡreceptor is essential in signaling pathway.There has no report about the effect of dyslipidemia on the expression of TGF-β2 and TGF-βtypeⅡreceptor in retina.
According to the research background above,the present study was designed to investigate the effects of lipid on the expression of TGF-β2 and its receptor(typeⅡ) and the apoptosis of retinal endothelial cells in retina.
Chapter 1.The effects of high fat diet ingestion on the expressions of retinal TGF-β2 and TβRⅡin streptozotocin-induced diabetic rats
Objective To investigate the effects of high fat diet ingestion on retinal TGF-β2 and TβRⅡmRNA in streptozotocin-induced diabetic rats.Methods After high fat diet was given to diabetic rats for 24 weeks,the expressions of TGF-β2 and TβRⅡmRNA in retina of diabetic rats were determined by RT-PCR analysis.Results The level of TGF-β2 mRNA in diabetic rats was increased compared with non-diabetic rats(P＜0.01);The level of TGF-β2 mRNA in diabetic rats on high fat diet was significantly increased compared with that of diabetic rats on normal fat diet(P＜0.01);The level of TβRⅡmRNA was no significant difference among diabetic rats and non-diabetic rats on high fat diet or normal fat diet.Conclusion High fat diet ingestion can increase TGF-β2 mRNA expression in retina of diabetic rats,and has no effect on the expression of TβRⅡmRNA in retina.
Chapter 2.The effect of LPC on the apoptosis of bovine retinal endothelial cells
Objective To study whether LPC treatment can induce apoptosis of bovine retinal endothelial cells in vitro.Methods After the isolation of active retinal blood vessels,BRECs were cultured in the media of DMEM containing 20%fetal bovine serum and 5%human platelet-poor plasma and 20μl/ml retinal extract and were purified through separating and weeding for the colonies of cells in primary culture.BRECs were exposed to a rang of LPC concentrations(0-60 umol/L)and cultured in 6-well plates for 6,12,24 hours.Apoptosis was examined by acridine orange(AO) staining under fluorescence microscope.Flow cytometry was used to detect apoptosis rate.The intracellular content of calcium was determined with F-2000 type spectrofluorometer,and intracellular concentration of free calcium ion was calculated.Results BRECs with high purity can be obtained by using the media of DMEM contained 20 %fetal bovine serum,5%human platelet-poor plasma and 20μl/ml retinal extract and by separating and weeding for the colonies of cells in primary culture.After LPC treatment for 24 hours,the rate of apoptosis was significantly higher at LPC concentration 60umol/L compared to 20 or 40umol/L in bovine retinal endothelia cells.The concentration of free calcium ion was obviously elevated when the concentration of LPC from 20umol/L to 60umol/L,and the duration of LPC treatment had influence on concentration of free calcium ion,longer duration of LPC treatment had higher concerntration of free calcium ion.Conclusion Relative purity BRECs were attained and reproducible by using a selective cultural method.LPC treatment is able to increase the intracellular concentration of free calcium ion and to induce apoptosis of bovine retinal endothelial cells in a time and dose-dependment fashion.
Chapter 3.The effects of LPC on the expressions of TGF-β2 and TβRⅡin bovine retinal endothelial cells
Objective To investigate the the effects of LPC on the expressions of TGF-β2 and TβRⅡin bovine retinal endothelial cells.Methods Bovine retinal endothelial cells were isolated from bovine eyes,cultured in vitro and exposed to a rang of LPC concentration(0-60umol/L).The levels of TGF-β2 and TβRⅡmRNA were determined by RT-PCR and heminested RT-PCR analysis,respectively.Results RT-PCR showed the level of TβRⅡmRNA was significantly higher at LPC concentration 40umol/L compared to 20 or 60umol/L after 12 hours.Heminested RT-PCR showed that the change of LPC concentrations had no significant effect on the expression of TβRⅡmRNA.Conclusion These results demonstrate that LPC regulates TGF-β2 mRNA expression and has no significant effect on the level of TβRⅡmRNA in bovine retinal endothelial cells.
糖尿病视网膜病变(Diabetic Retinopathy,DR)是患者致盲的主要原因之一,其确切的发病机制尚不清楚,目前认为是多种因素协同作用的结果。在过去的几十年来对这种高葡萄糖导致的疾病的认识有很大的进展,但脂代谢紊乱在糖尿病微血管病变中的作用机制目前尚不清楚。临床观察表明脂代谢紊乱与糖尿病视网膜病变有密切关系,因此研究其作用机制就显得尤为重要。
DR的病理改变包括毛细血管闭塞,微动脉瘤形成,血管壁内周细胞的选择性丧失,基底膜的增厚和新生血管形成。在DR中,视网膜微血管内皮细胞、Muller细胞、神经节细胞、周细胞通过凋亡而丧失,这种情况在DR的早期就可出现,目前国内外还未见有关脂代谢紊乱与视网膜内皮细胞凋亡关系的相关报道。
新生血管形成与视网膜缺血关系密切,生长因子在其病理过程中起重要作用。缺血的视网膜能分泌生长因子,刺激残存的血管增殖。脂代谢紊乱导致DR的分子机制目前仍不清楚。TGF-β与内皮细胞的增殖、黏附和细胞外基质的聚积有关。在哺乳动物中,TGF-β有三种异构体,命名为TGF-β1、TGF-β2、TGF-γ3。TGF-β在眼组织中有广泛表达,其中在视网膜组织中主要表达TGF-β2。TGF-β作为一种具有双相功能的生长调节子,其刺激或抑制增殖的作用依赖细胞的培养条件、TGF-β的浓度及其他协同调节的细胞因子。TGF-β通过调节内皮细胞的增殖、移行,促进血管腔的形成和成熟而参与新生血管形成。
TGF-β通过与靶细胞表面的特异受体结合而发挥生物效应。细胞有表面的二种TGF-β受体(TβRⅠ、TβRⅡ),这二种受体的跨膜丝氨酸/苏氨酸部分通过形成受体复合物参与TGF-β的信号通路,从而调节TGF-β的效应,Ⅱ型受体的激酶活性是信号传导所必需的。目前还未见有关脂代谢紊乱对视网膜TGF-β2及其Ⅱ型受体影响的相关报道。
基于上述原因,本研究探讨脂毒性对视网膜TGF-β2、TβRⅡ表达及内皮细胞凋亡的影响。
第一章:高脂喂养对糖尿病大鼠视网膜TGF-β2与TβRⅡmRNA表达的影响
目的:探讨高脂喂养的糖尿病大鼠视网膜中TGF-β2及TβRⅡmRNA的表达。方法:应用RT-PCR方法检测高脂喂养的糖尿病大鼠视网膜中TGF-β2及TβRⅡmRNA的表达水平。结果:糖尿病大鼠视网膜中TGF-β2 mRNA的表达高于非糖尿病大鼠视网膜(P＜0.01);高脂喂养的糖尿病大鼠视网膜中TGF-β2 mRNA的表达高于普通喂养的糖尿病大鼠视网膜(P＜0.01);TβRⅡmRNA的表达水平在非糖尿病大鼠视网膜与糖尿病大鼠视网膜间比较无明显差异;高脂喂养的糖尿病大鼠视网膜中TβRⅡmRNA的表达水平与普通喂养的糖尿病大鼠间比较亦无明显差异。结论:高脂喂养的糖尿病大鼠视网膜中TGF-β2 mRNA的表达水平升高。高脂喂养对糖尿病大鼠视网膜中TβRⅡmRNA的表达无影响。
第二章溶血卵磷脂对牛视网膜微血管内皮细胞凋亡的影响
目的:探讨溶血卵磷脂(LPC)对牛视网膜微血管内皮细胞(BRECs)凋亡的影响。方法:视网膜微血管消化分离后,采用含20%胎牛血清、5%PPP和20μl/ml视网膜浸出液的DMEM培养基,结合原代细胞的分离、除杂培养BRECs。培养的BRECs中加入不同浓度的LPC(0～60umol/L),分别培养6小时、12小时、24小时,通过吖啶橙染色在荧光显微镜下观察细胞凋亡,流式细胞检测细胞凋亡率,F2000荧光分光光度计测细胞内钙离子浓度并计算游离钙浓度。结果:(1)含20%FBS的DMEM培养基中加入5%PPP及20μl/ml的视网膜浸出液,结合原代细胞克隆的分离、除杂,可获得较纯净的BRECs;(2)LPC浓度为60 umol/L作用BRECs 24小时后,BRECs凋亡率明显高于LPC浓度为20umol/L及40umol/L时;LPC浓度从20umol/L增加到60umol/L过程中,细胞内游离钙离子浓度明显增加,而且细胞内游离钙离子浓度的增加与LPC的作用时间有关,作用时间越长,钙离子浓度越高。结论:(1)通过选择性培养能获得高纯度的BRECs,并能连续传代;(2)LPC能增加细胞内游离钙离子浓度,促使BREC的凋亡,而且LPC的这种作用具有时间和剂量依赖性。
第三章:LPC对牛视网膜微血管内皮细胞TGF-β2与TβRⅡmRNA表达的影响
目的:探讨不同浓度的LPC对牛视网膜微血管内皮细胞TGF-β2与TβRⅡmRNA表达的影响。方法:原代分离、培养牛的视网膜微血管内皮细胞,加入不同浓度的LPC(0～60umol/L),分别培养6小时、12小时、24小时,RT-PCR检测TGF-β_2 mRNA表达水平,半巢式RT-PCR检测TβRⅡmRNA的表达水平。结果:RT-PCR结果表明,LPC浓度为40umol/L作用12小时后,TGF-β2 mRNA水平明显高于LPC浓度为20 umol/L和60umol/L;LPC浓度改变对TβRⅡmRNA的表达无明显影响。结论:LPC能调节牛视网膜内皮细胞TGF-β2的表达;LPC对牛视网膜内皮细胞TβRⅡ的表达无明显影响;
Research background
Diabetic retinopathy is one of the important cause of visual disability in diabetic subjects,its precisely mechanism is not yet fully understood, and recognized as the result of multiple factors synergistic action.Despite considerable progress in understanding of hyperglycemia-induced disease over the past decade,the link between lipid metabolic disorders and retinopathy still eludes us.Clinical observations have shown that there is a intimate link between lipid metabolic disorders and retinopathy,so it is important to investigate the mechanism by which lipid leads to diabetic retinopathy.
Diabetic retinopathy is characterized by capillary occlusions, microaneurysms,selective loss of intramural pericytes,acellular capillaries,thickening of the basement membrane,and finally, angiogenesis and neovascularization.In the pathogenesis of retinopathy in diabetes,retinal microvascular endothelial,Muller cell,and ganglion cells and pericytes are lost selectively via apoptosis before other histopathology is detectable.It is not reported Whether dyslipidemia can induce the apoptosis of retinal endothelial cells.
Neovascularization is strongly associated with retinal ischaemia, and growth factors have been implicated in its pathogenesis.The ischaemic retina is assumed to secrete growth factors which stimulate residual vessels to proliferate.The molecular mechanisms of dyslipidemia leading to diabetic retinopathy have not been studied in detail.Transforming growth factor beta(TGF-β) is involved in endothelial cell proliferation,adhesion,and deposition extracellular maxtrix.There has three well-defined mammalian isoforms,numerically designated as TGF-β1-3,eye tissue extensively expresses TGF-β, principally TGF-β2 in retina tissue.TGF-βacts as a bifunctional regulator of growth and it may either stimulate or inhibit proliferation depending on cell culture condition,TGF-βconcentration,or other cytokine.TGF-βis able to regulate angiogenesis by the regulation of endothelial cell growth and migration and the promotion of tube formation and vessel maturation.
TGF-βexerts its biological effects by binding to specific cell surface receptors on target cells.Two cell surface TGF-βreceptor(TβRⅠ,TβRⅡ) proteins regulate the effects of TGF-βand the complex consisting of the typeⅠand typeⅡtransmembrane serine / threonine participates in signaling pathway and kinase activity of the typeⅡreceptor is essential in signaling pathway.There has no report about the effect of dyslipidemia on the expression of TGF-β2 and TGF-βtypeⅡreceptor in retina.
According to the research background above,the present study was designed to investigate the effects of lipid on the expression of TGF-β2 and its receptor(typeⅡ) and the apoptosis of retinal endothelial cells in retina.
Chapter 1.The effects of high fat diet ingestion on the expressions of retinal TGF-β2 and TβRⅡin streptozotocin-induced diabetic rats
Objective To investigate the effects of high fat diet ingestion on retinal TGF-β2 and TβRⅡmRNA in streptozotocin-induced diabetic rats.Methods After high fat diet was given to diabetic rats for 24 weeks,the expressions of TGF-β2 and TβRⅡmRNA in retina of diabetic rats were determined by RT-PCR analysis.Results The level of TGF-β2 mRNA in diabetic rats was increased compared with non-diabetic rats(P＜0.01);The level of TGF-β2 mRNA in diabetic rats on high fat diet was significantly increased compared with that of diabetic rats on normal fat diet(P＜0.01);The level of TβRⅡmRNA was no significant difference among diabetic rats and non-diabetic rats on high fat diet or normal fat diet.Conclusion High fat diet ingestion can increase TGF-β2 mRNA expression in retina of diabetic rats,and has no effect on the expression of TβRⅡmRNA in retina.
Chapter 2.The effect of LPC on the apoptosis of bovine retinal endothelial cells
Objective To study whether LPC treatment can induce apoptosis of bovine retinal endothelial cells in vitro.Methods After the isolation of active retinal blood vessels,BRECs were cultured in the media of DMEM containing 20%fetal bovine serum and 5%human platelet-poor plasma and 20μl/ml retinal extract and were purified through separating and weeding for the colonies of cells in primary culture.BRECs were exposed to a rang of LPC concentrations(0-60 umol/L)and cultured in 6-well plates for 6,12,24 hours.Apoptosis was examined by acridine orange(AO) staining under fluorescence microscope.Flow cytometry was used to detect apoptosis rate.The intracellular content of calcium was determined with F-2000 type spectrofluorometer,and intracellular concentration of free calcium ion was calculated.Results BRECs with high purity can be obtained by using the media of DMEM contained 20 %fetal bovine serum,5%human platelet-poor plasma and 20μl/ml retinal extract and by separating and weeding for the colonies of cells in primary culture.After LPC treatment for 24 hours,the rate of apoptosis was significantly higher at LPC concentration 60umol/L compared to 20 or 40umol/L in bovine retinal endothelia cells.The concentration of free calcium ion was obviously elevated when the concentration of LPC from 20umol/L to 60umol/L,and the duration of LPC treatment had influence on concentration of free calcium ion,longer duration of LPC treatment had higher concerntration of free calcium ion.Conclusion Relative purity BRECs were attained and reproducible by using a selective cultural method.LPC treatment is able to increase the intracellular concentration of free calcium ion and to induce apoptosis of bovine retinal endothelial cells in a time and dose-dependment fashion.
Chapter 3.The effects of LPC on the expressions of TGF-β2 and TβRⅡin bovine retinal endothelial cells
Objective To investigate the the effects of LPC on the expressions of TGF-β2 and TβRⅡin bovine retinal endothelial cells.Methods Bovine retinal endothelial cells were isolated from bovine eyes,cultured in vitro and exposed to a rang of LPC concentration(0-60umol/L).The levels of TGF-β2 and TβRⅡmRNA were determined by RT-PCR and heminested RT-PCR analysis,respectively.Results RT-PCR showed the level of TβRⅡmRNA was significantly higher at LPC concentration 40umol/L compared to 20 or 60umol/L after 12 hours.Heminested RT-PCR showed that the change of LPC concentrations had no significant effect on the expression of TβRⅡmRNA.Conclusion These results demonstrate that LPC regulates TGF-β2 mRNA expression and has no significant effect on the level of TβRⅡmRNA in bovine retinal endothelial cells.
引文
[1] McGarry JD. Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes, 2002,51(1):7-18
[2] Sivitz WI. Lipotoxicity and glucotoxicity in type 2 diabetes.Effects on development and progression. Postgrad Med, 2001 ,109(4):55-9, 63-4
[3] Biljana M, Robert JG, David MN,JoAnn EManson,et al .A Prospective Study of Serum Lipids and Risk of Diabetic Macular Edema in Type 1 Diabetes. Diabetes, 2004,53: 2883-2892
[4] Timothy JL, Alicia JJ, Deyi Z, et al.Diabetic retinopathy and serum lipoprotein subclasses in the DCCT/EDIC cohort.IVOS, 2004,45(3):910-18
[5] Leung H, Wang JJ, Rochtchina E, Wong TY,et al Dyslipidaemia and Microvascular disease in the retina . Eye, 2005, 19, 861-868
[6] Larsson LI, Alm A, Lithner F, Dahlen G, Bergstrom R. The association of hyperlipidemia with retinopathy in diabetic patients aged 15-50 years in the county of Umea. Acta Ophthalmol Scand, 1999 ,77(5):585-91
[7] Cusick M,Chew EY,et al. Histopathology and regression of retinal hard exudat.es in diabetic retinopathy after reduction of elevated serum lipid levels. Phthalmology, 2003, 110(11):2126 33
[8] Mandarino U, Finlayson J, Hassell JR. High glucose down regulates glucose transport activity in retinal capillary pericytes but not endothelial cells. Invest Ophthalmol Vis Res, 1994,35(8):964-972
[9] Podesta F, Romeo G, Liu WH, et al. Bax is increased in the retina of diabetic subjects and is associated with pericyte apoptosis in vivo and in vitro.Am J Pathol, 2000, 156(3):1025-32
[10] Li W, Yanoff M, Liu X, Ye X. Retinal capillary pericyte apoptosis in early human diabetic retinopathy.Chin Med J (Engl), 1997, 110(9):659-63
[11]Mizutani M,Kern TS,Lorenzi M.Accelerated death of retinal microvascular cells in human and experimental diabetic retinopathy.J Clin Invest,1996,97(12):2883-90
[12]刘学政,萧鸿,曲维新,等.糖尿病大鼠视网膜毛细血管细胞凋亡及其凋亡相关基因的表达.中华眼科杂志,2001,37(1):59-62
[13]Beltramo Z,Berrone E,Buttiglieris,Porta M.Thiamine and benfotiamineprevent increased apoptosis in endothelial cells and pericytes cultured in high glucose.Diabetes Metab Res Rev,2004,20(4):330-336
[14]Jump DB.Dietary polyunsaturated fatty acids and regulation of gene transcription.Curr Opin Lipidol.2002,13(2):155-164
[15]Jump DB.TThe biochemistry of n-3 polyunsaturated fatty acids.J Biol Chem.2002,277(11):8755-8
[16]胡俊斌,魏文宁,丁桂芝,等.糖尿病患者凝血与纤溶状态初探.中华内分泌代谢杂志,1996,12:118-119
[17]wiedfmann P.Growth factors in retinal diseases:proliferative vitreoretinopathy,proliferative diabetic retinopathy and retinal degeneration.Surv Ophthalmol,1992,36(5):373-384
[18]Pfeiffer A,Middelberg-Bisping K,Drewes C,Schatz H..Elevated plasma levels of transforming growth factor-beta 1 in NIDDM.Diabetes Care,1996,19(10):1113-7
[19]Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease:the Scandinavian Simvastatin Survival Study(4S).Lancet,1994,344(8934):1383-9
[20]Derynck R,Zhang YE.Smad-dependent and Smad-independent pathways in TGF-beta family signalling.Nature,2003,425(6958):577-84
[21]Esser P,Bartz-Schmidt KU,Walter P,Kaszli F,Heimann K,Weller M.Apoptotic cell death in proliferative vitreoretinopathy.Ger J Ophthalmol,1996,5(2):73-8
[22]El Ghrably I,Powe DG,Orr G,Fischer D,et al.Apoptosis in proliferative vitreoretinopathy.Invest Ophthalmol Vis Sci.2004,45(5):1473-9
[23]Spirin KS,Saghizaden M,Lewin SL,etal.Basement membrane and growth factor gene expression in normal and diabetic human retinal.Curr Eye Res,1999,18(6):490-499.
[24]Hosoda Y,Okada M,Matsumura M,et al,Intravitreal neo-vascular tissue of proliferative diabetic retinopathy:an immunohistochemical study.Ophthalmic Res,1992,24(5):260-264
[25]Porreca E,Di Febbo C,Baccante G,et al.Increased transforming growth factor-beta(1) circulating levels and production in human monocytes after 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase inhibition with pravastatin.J Am Coll Cardiol,2002,39(11):1752-7
[26]Muhlfeld AS,Spencer MW,Hudkins KL,Kirk E,LeBoeuf RC,Alpers CE.Hyperlipidemia aggravates renal disease in B6.ROP Os/+ mice.Kidney Int.2004,66(4):1393-402
[27]Ryu JK,Han JY,Chu YC,et at.Expression of cavernous transforming growth factor-betal and its type Ⅱ receptor in patients with erectile dysfunction.Int J Androl,2004,27(1):42-9
[28]Natarajan R,Gerrity RG,Gu JL,Lanting L,Thomas L,Nadler JL.Role of 12-lipoxygenase and oxidant stress in hyperglycaemia-induced acceleration of atherosclerosis in a diabetic pig model.Diabetologia,2002,45(1):125-33
[29]Sen K,Misra A,Kumar A,Pandey RM,Simvastatin retards progression of retinopathy in diabetic patients with hypercholesterolemia.Diabetes Res Clin Pract,2002,56(1):1-11
[30]Hirase K,IkedaT,Sotozono C,etal.Transforming growth factor-β2 in the vitreous in proliferative diabetic retinopathy.ArchOphthalmol,1998,116(6):738-741
[31]沈炜,柳林,满晓波,刘志勇,李慎菁.实时荧光聚合酶链反应定量检测大鼠视网膜中转化生长因子β1和β2的表达.中华眼底病杂志,2005,21(1):48-49
[32]Obata H,Kaburaki T,Kato M,Yamashita H.Expression TGF-beta type Ⅰand typeⅡreceptors in rat eyes.Curr Eye Res,1996,15(3):335-340
[33]Ochiai Y,Ochiai H.Higher concentration of transforming growth factor-beta in aqueous humor of gIaucomatous eyes and diabetic eyes.JPN Ophthalmol,2002,46(3):249-253
[34]Matsumoto Y,Takahashi M,Ogata M.Relationship between glycoxidation and cytokines in the vitreous of eyes with diabetic retinopathy.JPN Ophthalmol,2002,46(4):406-412
[35]Bochaton-Piallat ML,Kapetanios AD,Donati G,et al.TGF-betal,TGF-beta receptor Ⅱ and ED-A fibronectin expression in myofibroblast of vitreoretinopathy.Invest Ophthalmol Vis Sci,2000,41(8):2336-42
[36]Spirin KS,Saghizaden M,Lewin SL,etal.Basement membrane and growth factor gene expression in normal and diabetic human retinal.Curr Eye Res,1999,18(6):490-499
[37]Hosoda Y,Okada M,Matsumura M,et al.Intravitreal neo-vascular tissue of proliferative diabetic retinopathy:an immuno-histoche-mical study.Ophthalmic Res,1992,24(5):260-264
[38]Klein BE,Moss SE,Klein R,et al.The Wisconsin epidemioiogic study of diabetic retinopathy.Relationship of serum cholesterol to retinopethy and bard exudates.Ophthalmology,1991,98(8):1261-65
[39]张胜兰,等.糖尿病患者红细胞变形能力受损.中华内分泌代谢志,1989,5(2):95-96
[40]Eisenstein R,Grant BD.Growth inhibitory activities in a vascular tissues are recognized by anti transforming growth factor β antibodies.Curr Eye Res,1991,10(2):157-162
[41]Hollbom M,Kohen L,Wiedemann P,Enzmann V.The influence of proinflammatory cytokines on human retinal pigment epithelium cell receptors.Graefes Arch Clin Exp Ophthalmology,2001,239(4):294-301
[42]Monique M,Pascal JV,et al.Glucose-mediated regulation of transfo-rming growth factor-beta(TGF-β) and TGF-βreceptor in human retinal endothial cells.Current Eye Res,1999,19(2):162-170
[43]郭长梅,惠延年,马吉献,等.转化生长因子β受体Ⅱ在增生性玻璃体视网膜病变增生膜中的表达.眼科学报,2003,19(4):244-247.
[44]Bert MG,Patrcia AD,Ronald G,et al.Demonstration of vasoproliferative activity from mammalian retina.Cell Biology,1980,84: 298-304
[145]夏欣,许迅,顾青.牛视网膜微血管内皮细胞和周细胞的体外培养.中华眼底病杂志,2004,20(1):23-26
[46]席兴华,姜德咏,唐罗生.牛视网膜微血管周细胞和内皮细胞的选择性培养.眼科研究,2000,18(6):493-496
[47]Cohen RA,Hennekens CH,Christen WG,et al.Determinants of retinopathy progression in type 1 diabetes mellitus.Am Med,1999,107(1):45-51
[48]Li W,Liu X,et,al.Cultured retinal capillary pericytes die by apoptosis after an abrupt fluctuation from hyperglycemic levels:a comparative study with retinal capillary endothelial cells.Diabetologia,1996,39:537-541
[49]Schonfelder U,Hofer A,Paul M,Funk RH.In situ observation of living pericytes in rat retinal capillaries.Microvasc Res,1998,56(1):22-9.
[50]Song W,Barth JL,Lu K,et al.Effects of modified low-density lipoproteins on human retinal pericyte survival.Ann N Y Acad Sci.2005,1043:390-5.
[51]Sellmayer A,Hrboticky N,Weber PC.Lipids in vascular function.Lipids,1999,34(suppl):S13 -S18.
[52]Berliner JA,Heinecke JW.The role of oxidized lipoproteins in atherogenesis.Free Raddic Biol Med,1996,20(5):707-708
[53]Yokoyama M,Hirata KI,Miyake R,et al.LysophoPhatidylcholine:Essential role in the inhibition of endothelium dependent vasorelaxation by oxidized low density lipoprotein.Biochem Biophy Resea Commun,1990,168(1):301-303
[54]Schaefer CA,Kuhlmann CR,Gast C,et al.Statins prevent oxidized low-density lipoprotein- and lysophosphatidylcholine-induced proliferation of human endothelial cells.Vascul Pharmacol.2004,41(2):67-73
[55]Dulak J,Jozkowicz A,Dichtl W,et al.Vascular endothelial growth factor synthesis in vascular smooth muscle cells is enhanced by 7 ketocholesterol and lysophosphatidylcholine independently of their effect on nitric oxide generation.Atherosclerosis,2001,159(2):325-32
[56]Sata M,Walsh K.Endothelial cell apoptosis induced by oxidized LDL is associated with the down-regulation of the cellular caspase inhibitor FLIP.J Biol Chem,1998,273(50):33103-33106
[57]Heiloth A,Heermeier K,et al.Stimulation of NADPH oxidase by oxidized low-density lipoprotein induces proliferation of human vascular endothelial cells.Am Soc Nephrol,2000,11(10):1819-1825
[58]Rymaszewski Z,Szymanski PT,et al.Human retinal Vascular cells differ from umbilical cells in synthetic functions and their response to glucose.PSEBM,1992,199(2):183-191
[59]马建芳,杨中汉,宋志宏,等.大利量葡萄糖诱导人视网膜内皮细胞凋亡.第一军医大学学报,2003,23(5):435-438
[60]Bucala R.Mitchell R.Arnold K.et al.Identification of the major site of apolipoprotein B modification by advanced glycosylation end products blocking uptakeby the low density lipoprotein receptor.J Biol Chem,1995,270(18):10828-10832
[61]Jump DB.The biochemistry of n-3 polyunsaturated fatty acids.J Biol Chem,2002,277(11):8755-8
[62]Lauritzen T,Frost-Larsen K,et al.Effect of one year of near-normal blood glues levels on retinopathy in insulin-dependent diabetics.Lancet,1983,1:2000-2004
[63]Kenne WF,The role of lipids in renal disease:future challenges.Kidney Int,2000:57(Suppl):S27-31
[64]Tedgui A,Mallat Z.Anti-inflammatory mechanisms in the vascular wall.Circ Res,2001,88(9):877-87
[65]Pintavorn P,Ballermann BJ.TGF-beta and the endothelium during immune injury.Kidney Int,1997,51(5):1401-12
[66]Pepper MS.Transforming growth factor-beta:vasculogenesis,angiogenesis,and vessel wall integrity.Cytokine Growth Factor Rev.1997,8(1):21-43
[67]Robertson AK,Rudling M,Zhou X,et al.Disruption of TGF-beta signaling in T cells accelerates atherosclerosis.J Clin Invest, 2003,112(9):1342-50
[68]Sanford LP,Ormsby I,Gittenberger-de Groot AC,et al.TGFbeta2knockout mice have multiple developmental defects that are non-overlapping with other TGF beta knockout phenotypes.Development,1997,124(13):2659-70
[69]Oh SP,Seki T,Goss KA,Imamura T,et al.Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis.Proc Natl Acad Sci U S A.2000,97(6):2626-31
[70]Galvin KM,Donovan MJ,Lynch CA,et al.A role for smad6 in development and homeostasis of the cardiovascular system.Nat Genet,2000,24(2):171-4
[71]Sohn M,Tan Y,Klein RL,Jaffa AA.Evidence for low-density lipoprotein-induced expression of connective tissue growth factor in mesangial cells.Kidney Int,2005,67(4):1286-1296
[72]Lassila M,Seah KK,Allen TJ,et al.Accelerated nephropathy in diabetic apolipoprotein e-knockout mouse:role of advanced glycation end products.J Am Soc Nephrol.2004,15(8):2125-38
[73]Muhlfeld AS,Spencer MW,Hudkins KL,Kirk E,LeBoeuf RC,Alpers CE.Hyperlipidemia aggravates renal disease in B6.ROP Os/+ mice.Kidney Int,2004,66(4):1393-402
[74]Chen YL,Wu HW,Jiang MJ.Transforming growth factor-betal gene and protein expression associated with atherogenesis of cholesterol-fed rabbits.Histol Histopathol,2000,15(2):421-8
[75]RayChaudhury A,D'Amore PA.Endothelial cell regulation by transforming growth factor-beta.J Cell Biochem.1991,47(3):224-9
[76]Leksa V,Godar S,Schiller HB,Fuertbauer E,et al.TGF-beta-induced apoptosis in endothelial cells mediated by M6P/IGFII-R and mini-plasminogen.Cell Sci,2005,118(19):4577-86
[77]Antonelli Orlidge A,Saunders KB,Smith SR,D'Amore PA.An activated form of transforming growth factor beta is preduced by cocultures of endothelial cells and pericytes.Proc Natl Acad Sci U S A,1989,86(12):4544-8
[78] Wakefield LM, Smith DM, Flanders KC, Sporn MB. Latent transforming growth factor-beta from human platelets. A high molecular weight complex containing precursor sequences. J Biol Chem, 1988,263(16) :7646-54
[79] Lyons RM, Keski-Oja J, Moses HL. Proteolytic activation of latent transforming growth factor-beta from fibroblast-conditioned medium. J Cell Biol, 1988, 106(5):1659-65
[80] Flaumenhaft R,Abe M, Mignatti P, et al. Basic fibroblast growth factor-induced activation of transforming growth factor beta in endothelial cell regulation of plasminogen activator activity.J Cell Biol, 1992, 118(4):901-9
[81] Knott RM, Muckersie E, Robertson M, Forrester JV. Glucose-dependent regulation of DNA synthesis in bovine retinal endothelial cells.Curr Eye Res, 1998 ,17(1):1-8
[82] Ishida K, Yamashita H, Katagiri H, Oka Y. Regulation of glucose transporter 1 (GLUT1) gene expression by epidermal growth factor in bovine corneal endothelial cells. Jpn J Ophthalmol.1995, 39(3): 225-32
[83] Sohn M, Tan Y, Wang B, Klein RL, et al. Mechanisms of low-density 1 ipoprotein-induced expression of connective tissue growth factor in human aortic endothelial cells. Am J Physiol Heart Circ Physiol,2006 ,290(4):H1624-34
[84] Saura M, Zaragoza C, Herranz B, et al. Nitric oxide regulates transforming growth factor-beta signaling in endothelial cells.Circ Res, 2005,97(11):1115-23
[85] Hu T, Ramachandrarao SP, Siva S, et al.Reactive oxygen species production via NADPH oxidase mediates TGF-beta-induced cytoskeletal alterations in endothelial cells. Am Physiol Renal Physiol,2005, 289(4):816-825
[86] NorataGD, Callegari E, Marchesi M, et al. High-density lipoproteins induce transforming growth factor-beta2 expression in endothelial cells. Circulation, 2005, 111(21) :2805-281i
[87] Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling.Nature,2003,425(6958):577-84
[88]Raul AP,Janice AJ,Bert MG.Effects of TGF-βandTGF-βneutralizing antibodies on the fibroblast-induced collagen gel contraction:implications for proliferative vitreoretinopathy.Invest Ophthalmol Vis Sci,1994,35(7):2804-2809
[1]McGarry JD.Banting lecture 2001:dysregulation of fatty acid metabolism in the etiology of type 2 diabetes.Diabetes,2002,51(1):7-18
[2]Sivitz WI.Lipotoxicity and glucotoxicity in type 2 diabetes.Effects on development and progression.Postgrad Med,2001,109(4):55-9,63-4
[3]Chowdhury TA,Hopkins D,Dodson PM,Vafidis GC.The role of serum lipids in exudative diabetic maculopathy:is there a place for lipid lowering therapy?Eye,2002,6(6):689-93
[4]Ravid M,Brosh D,Ravid-Safran D,Levy Z,Rachmani R.Main risk factors for nephropathy in type 2 diabetes mellitus are plasma cholesterol levels,mean blood pressure,and hyperglycemia.Arch Intern Med,1998,158(9):998-1004
[5]Hadjadj S,Pean F,Gallois Y,et al.Different patterns of insulin resistance in relatives of type 1 diabetic patients with retinopathy or nephropathy:the Genesis France-Belgium Study.Diabetes Care,2004,27(11):2661-68
[6]Coppack SW,Evans RD,Fisher RM,et al.Adipose tissue metabolism in obesity:lipase action in vivo before and after a mixed meal.Metabolism,1992,41(3):264-72
[7]Weinstock PH,Levak-Frank S,Hudgins LC,Radner H,Friedman JM,Zechner R,Breslow JL.Lipoprotein lipase controls fatty acid entry into adipose tissue,but fat mass is preserved by endogenous synthesis in mice deficient in adipose tissue lipoprotein lipase.Proc Natl Acad Sci U S A,1997,94(19):10261-6
[8]Goldberg RB.Lipid disorders in diabetes.Diabetes Care,1981,4(5):561-72.
[9]Goldberg RB,Capuzzi D.Lipid disorders in type 1 and type 2 diabetes.Clin Lab Med,2001,21(1):147-72
[10]Goldberg IJ.Clinical review 124:Diabetic dyslipidemia:causes and consequences.J Clin Endocrinol Metab,2001,86(3):965-71
[11]Poisson JP.Essential fatty acid metabolism in diabetes.Nutrition,1989,5(4):263-6
[12]Rossetti L,Goldberg IJ.A new piece in the diabetes puzzle.Nat Med,2002,8(2):112-4
[13]Vessby B.Dietary fat and insulin action in humans.Br Nutr,2000,83(suppl 1):S91-S96
[14]Zenobi PD,Holzmann P,Glatz Y,Riesen WF,Froesch ER.Improvement of lipid profile in type 2(non-insulin-dependent) diabetes mellitus by insulin-like growth factor I. Diabetologia,1993,36(5):465-9
[15] McGarry JD. What if Minkowski had been ageusic? An alternative angle on diabetes. Science, 1992,258(5083):766-70
[16] Larsson LI, Alm A, Lithner F, Dahlen G, Bergstrom R. The association of hyperlipidemia with retinopathy in diabetic patients aged 15-50 years in the county of Umea.Acta Ophthalmol Scand ,1999,77(5):585-591
[17] Natarajan R, Gerrity RG, Gu JL, Lanting L, Thomas L, Nadler JL. Role of 12-lipoxygenase and oxidant stress in hyperglycaemia-induced acceleration of atherosclerosis in a diabetic pig model, Diabetologia. 2002 Jan;45(1):125-33.
[18] Sen K, Misra A, Kumar A, Pandey RM. Simvastatin retards progression of retinopathy in diabetic patients with hypercholesterolemia,Diabetes Res Clin Pract, 2002, 56 (1) : 1-11
[19] Cusick M, Chew EY, et al. Histopathology and regression of retinal hard exudates in diabetic retinopathy after reduction of elevated serum lipid leveis. Phthalmology, 2003, 110(11):2126-2133
[20] Gupta A, Gupta V, Thapar S, Bhansali A. Lipid-lowering drug atorvastatin as an adjunct in the management of diabetic macular edema. Am Ophthalmol, 2004 ,137(4):675-82
[21] Klein R, Marino EK, Kuller LH, Polak JF, Tracy RP, Gottdiener JS, Burke GL, Hubbard LD, Boineau R. The relation of atherosclerotic cardiovascular disease to retinopathy in people with diabetes in the Cardiovascular Health Study.Br J Ophthalmol, 2002 ,86(1):84-90.
[22] Ferris FL 3rd, Chew EY, Hoogwerf BJ. Serum lipids and diabetic retinopathy. Early Treatment Diabetic Retinopathy Study Research Group.Diabetes Care, 1996,19(11):1291-3
[23] Chew EY, Klein ML, Ferris FL 3rd, Remaley NA, Murphy RP, Chantry K, Hoogwerf BJ, Miller D. Associat ion of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy. Early Treatment Diabetic Retinopathy Study (ETDRS) Report 22. Arch Ophthalmol, 1996,114(9):1079-84
[24]van Leiden HA,Dekker JM,Moll AC,Nijpels G,Heine RJ,Bouter LM,Stehouwer CD,Polak BC.Risk factors for incident retinopathy in a diabetic and nondiabetic population:the Hoorn study.Arch Ophthalmol,2003,121(2):245-51
[25]Klein BE,Moss SE,Klein R,et al,The Wisconsin epidemiologic study of diabetic retinopathy.Relationship of serum cholesterol to retinopethy and hard exudates.Ophthalmology,1991,98(8):1261-65
[26]Fernandez-Robredo P,Moyn D,et al.Vitamins C and e reduce retinal oxidative stress and nitric oxide metabolites and prevent ultrastructural alterations in porcine hypercholesterolemia.Invest Ophthalmol Vis Sic,2005,46(4):1140-1146
[27]Leung H,Wang JJ,Rochtchina E,et al.Dyslipidaemia and microvascular disease in the retina.Eye,2005,19(8):861-868
[28]Yamakawa K,Bhutto IA,Lu Z,Watanabe Y,Amemiya T.Retinal vascular changes in rats with inherited hypercholesterolemia corrosion cast demonstration.Curr Eye Res,2001,22(4):258-65
[29]张胜兰,等.糖尿病患者红细胞变形能力受损.中华内分泌代谢杂志,1989,5(2):95-96
[30]Coulon J,Willems D,Dorchy H.Increase in C-reactive protein plasma levels during diabetes in infants and young adults.Presse Med,2005,34(2 Pt 1):89-93
[31]Chen W,Jump DB,et al.Dyslipidemia,but not hyperglycemia,induces inflammatory adhesion molecules in human retinal vascular endothelial cells.Invest Ophthalmol Vis Sci,2003,44(11):5016-22
[32]Miyamoto K,Ogura Y.Pathogenetic potential of leukocytes in diabetic retinopathy.Semin Ophthalmol,1999,14(4):233-9
[33]Miyamoto K,Khosrof S,Bursell SE,Rohan R,Murata T,Clermont AC,Aiello LP,Ogura Y,Adamis AP.Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition.Proc Natl Acad Sci U S A,1999,96(19):10836-41
[34]胡俊斌,魏文宁,丁桂芝,等.糖尿病患者凝血与纤溶状态初探.中华内分泌 代谢杂志,1996,12:118-119
[35]汪崇文,郑汉莲,石俊等.2型糖尿病脂质代谢紊乱与视网膜病变相互关系研究.中华医学杂志,2001,25(1):36-37
[36]Darland DC,Massingham LJ,et al.Pericyte production of cellassociated VEGF is differentiation-dependent and is associated with endothelial survival.Dev Biol,2003,264(1)275-288
[37]Cohen RA,Hennekens CH,Christen WG,et al.Determinants of retinopathy progression in type 1 diabetes mellitus.Am Med,1999,107(1):45-51
[38]Li W,Liu X,Yanoff M,Cohen S,Ye X.Cultured retinal capillary pericytes die by apoptosis after an abrupt Fluctuation from high to low glucose levels:a comparative study with retinal capillary endothelial cells.Diabetologia,1996,39(5):537-47
[39]Yatoh S,Mizutani M,et al.Antioxidants and an inhibitor of advanced glycation ameliorate death of retinal microvascular cells in diabetic retinopathy.Diabetes Metab Res Rev,2006,22(1):38-45
[40]Lecomte M,Denis U,Ruggiero D,et al.Involvement of caspase-10in advanced glycation end-product-induced apoptosis of bovine retinal pericytes in culture.Biochim Biophys Acta,2004,1689(3):202-11
[41]Dagher Z,Park YS,et al.Studies of rat and human retinas predict a role for the polyol pathway in human diabetic retinopathy.Diabetes,2004,53(9):2404-11
[42]Schonfelder U,hofer A,Paul M,Funk RH.In situ observation of living pericytes in rat retinal capillaries.Microvasc Res,1998,56(1):22-9.
[43]Podesta F,Romeo G,Liu WH,Krajewski S,Reed JC,Gerhardinger C,Lorenzi M.Bax is increased in the retina of diabetic subjects and is associated with pericyte apoptosis in vivo and in vitro.Am J Pathol,2000,156(3):1025-32
[44]Li W,Yanoff M,Liu X,Ye X.Retinal capillary pericyte apoptosis in early human diabetic retinopathy.Chin Med.I(Engl),1997,110 (9):659-63
[45]Song W,Barth JL,Lu K,Yu Y,Huanz Y,Gittinger CK,Argraves WS,Lyons TJ.Effects of modified low-density lipoproteins on human retinal pericyte survival.Ann N Y Acad Sci,2005,1043:390-5
[46]Lupo G,Anfuso CD,Ragusa N,et al.t-Butyl hydroperoxide and oxidized low density lipoprotein enhance phospholipid hydrolysis in lipopolysaccharide- stimulated retinal pericytes.Biochim Biophys Acta,2001,1531(1-2):143-155
[47]Mizutani M,Kern TS,Lorenzi M.Accelerated death of retinal microvascular cells in human and experimental diabetic retinopathy.J Clin Invest,1996,97(12):2883-90
[48]刘学政,萧鸿,曲维新,等.糖尿病大鼠视网膜毛细血管细胞凋亡及其凋亡相关基因的表达.中华眼科杂志,2001,1:59-62
[49]Beltramo Z,Berrone E,Buttiglieris,Porta M.Thiamine and benfotiamine prevent increased apoptosis in endothelial cells and pericytes cultured in high glucose.Diabetes Metab Res Rev,2004,20(4):330-336
[50]Jump DB.Dietary polyunsaturated fatty acids and regulation of gene transcription.Curt Opin Lipidol,2002,13(2):155-64
[51]Jump DB.The biochemistry of n-3 polyunsaturated fatty acids.J Biol Chem,2002,277(11):8755-8
[52]Sellmayer A,Hrboticky N,Weber PC.Lipids in vascular function.hipids,1999,34(suppl):S13-S18
[53]Aiello LP,Avery RL,Arrigg PG,et al.Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders.N Engl J Med,1994,331(22):1480-7.
[54]Miller JW,Adamis AP,Aiello LP.Vascular endothelial growth factor in ocular neovascularization and proliferative diabetic retinopathy.Diabetes Metab Rev,1997,13(1):37-50
[55]Sharp PS.The role of growth factors in the development of diabetic retinopathy.Metabolism,1995,44(10 Suppl 4):72-5
[56]Pfeiffer A,Middelberg-Bisping K,Drewes C,Schatz H..Elevated plasma levels of transforming growth factor-beta 1 in NIDDM. Diabetes Care, 1996, 19(10):1113-7
[57] Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet, 1994, 344(8934):1383-9
[58] Monique M, Pascal JV, et al. Glucose-mediated regulation of transforming growth factor-beta(TGF-β) and TGF-β receptor in human retinal endothial cells. Current Eye Res, 1999, 19(2):162-170
[59] Raul AP, Janice AJ, Bert MG. Effects of TGF-β andTGF-β neutralizing antibodies on the fibroblast-induced collagen gel contraction:implications for proliferative vitreoretinopathy.Invest Ophthalmol Vis Sci,1994, 35(7):2804-2809
[60] Massague J, Chen YG. Controlling TGF-beta signaling. Genes , 2000,14(6): 627-644
[61] Sanford LP, Ormsby I, Gittenberger-de Groot AC, et al. TGFbeta2 knockout mice have multiple developmental defects that are nonoverlapping with other TGFbeta knockout phenotypes. Development,1997,124(13):2659-70
[62] Antonelli-Orlidge A, Saunders KB, Smith SR, D'Amore PA. An activated form of transforming growth factor beta is produced by cocultures of endothelial cells and pericytes. Proc Natl Acad Sci U S A, 1989, 86 (12): 4544-8
[63] Wakefield LM, Smith DM, Flanders KC, Sporn MB. Latent transforming growth factor-beta from human platelets. A high molecular weight complex containing precursor sequences. J Biol Chem, 1988, 263(16):7646-54.
[64] Lyons RM , Keski-Oja J,ct al.Proteolytic activation of latent transforming growth factor beta in the control of epidermal proliferation. Cell Biol, 1998, 106:1659-1665
[65] Flaumenhaft R, Abe M, Mignatti P, et al. Basic fibroblast growth factor-induced activation of transforming growth factor beta in endothelial cell regulation of plasminogen activator activity.J Cell Biol, 1992,118(4):901-9
[66] Knott RM,Robertson M,et al.Glucose dependent regulation of D\A synthesis in bovine retinal endothelial cells.Curt Eye Res,1998,17:1-8
[67]Ishida K,Yamashita H,Katagiri H,Oka Y.Regulation of glucose transporter 1(GLUT1) gene expression by epidermal growth factor in bovine corneal endothelial cells.Jpn J Ophthalmol.1995,39(3):225-32
[68]Sohn M,Tan Y,Wang B,Klein RL,et al.Mechanisms of low-density lipoprotein-induced expression of connective tissue growth factor in human aortic endothelial cells.Am J Physiol Heart Circ Physiol,2006,290(4):H1624-34
[69]Saura M,Zaragoza C,Herranz B,et al.Nitric oxide regulates transforming growth factor-beta signaling in endothelial cells.Circ Res,2005,97(11):1115-23
[70]Hu T,Ramachandrarao SP,Siva S,et al.Reactive oxygen species production via NADPH oxidase mediates TGF-beta-induced cytoskeletal alterations in endothelial cells.Am Physiol Renal Physiol,2005,289(4):816-825
[71]Norata GD,Callegari E,MarchesiM,etal.High-density lipoproteins induce transforming growth factor-beta2 expression in endothelial cells.Circulation,2005,111(21):2805-2811
[72]Eisenstein R,GrantBD.Growth inhibitory activities in a vascular tissues arerecognized by antitransforming growth factor βantibodies.CurrEye Res,1991,10(2):157-162
[73]柳林,沈炜,刘志勇.转化生长因子β mRNA在糖尿病大鼠视网膜中的表达.中华眼科杂志,2003,39:46-47
[74]Wileman,Samantha M,Booth,et al.Regulation of plasminogen activation by TGF-β in cultured human retinal endothelial cells.British Ophthalmology,2000,84(4):417-422
[75]Grant MB,CaballeroS,Bush DM,Spoerri PE.Fibronectin fragments modulate human retinal capillary cell proliferation and migration.Diabetes,1998,47(8):1335-40
[76]Spirin KS,Saghizaden M,Lewin SL,etal.Basement membrane and growth factor gene expression in normal and diabetic human retinal.Curr Eye Res,1999,18(6):490-499.
[77]Hosoda Y,Okada M,Matsumura M,et al,Intravitreal neo-vascular tissue of proliferative diabetic retinopathy:an immunohistochemical study.Ophthalmic Res,1992,24(5):260-264
[78]Wiedemann P.Growth factors in retinal diseases:proliferative vitreoretinopathy,proliferative diabetic retinopathy,and retinal degeneration.Surv Ophthalmol,1992,36(5):373-84
[79]Pfeiffer A,Schatz H.Diabetic microvascular complications and growth factors.Exp Clin Endocri,1995,103(1):7-14
[80]Peer J,Fovverg R,Itin A,et al.Upregulated expression of vascular endothelial growth factor in proliferative diabetic retinopathy.Br Ophthalmol,1996,80(3):241-44
[81]Weller M,Fontana A.The failure of current immunotherapy for malignant giioma.Tumor-derived TGF-beta,T-cell apoptosis,and the immune privilege of the brain.Brain Res Brain Res Rev,1995,21(2):128-51.
[82]Derynck R,Zhang YE.Smad-dependent and Smad-independent pathways in TGF-beta family signalling.Nature,2003,425(6958):577-84
[83]Esser P,Bartz-Schmidt KU,Walter P,Kaszli F,Heimann K,Weller M.Apoptotic cell death in proliferative vitreoretinopathy.Ger J Ophthalmol,1996,5(2):73-8
[84]El Ghrably I,Powe DG,Orr G,Fischer D,et al.Apoptosis in proliferative vitreoretinopathy.Invest Ophthalmol Vis Sci.2004,45(5):1473-9
[85]Obata H,Kaburaki T,Kato M,Yamashita H.Expression TGF-beta type Ⅰ and typeⅡreceptors in rat eyes.Curr Eye Res,1996,15(3):335-340
[86]Zhu HJ,Burgess AW.Regulation of transforming growth factor beta signaling.Mol Cell Biol Res Commun,2001,4(6):321-330
[87]Chen RH,Ebner R,derynck R.inactivation of the type Ⅱ receptor cereals two receptor pathways for the diverse TGF-beta activities.Science,1993,260(5112):1335-8
[88] Sankar S, Mahooti-Brooks N, et al. Modulation of transforming growth factor beta receptor levels on microvascular endothelial cells during in vitro angiogenesis. Clin Invest, 1996, 97(6):1436-46
[89] Yingling JM, Wang XF, Bassing CH. Signaling by the transforming growth factor-beta receptors. Biochira Biophys Acta, 1995, 1242(2):115-36
[90] Segarini PR. TGF-beta receptors: a complicated system of multiple binding proteins. Biochim Biophys Acta, 1993, 1155(3):269-75
[91] Kenne WF, The role of lipids in renal disease:future challenges. Kidney Int , 2000:57(Suppl):S27-31
[92] Tedgui A, Mallat Z. Anti-inflammatory mechanisms in the vascular wall.Circ Res, 2001,88(9) :877-87
[93] Pintavorn P,Ballermann BJ. TGF-beta and the endothelium during immune injury. Kidney Int,1997,51(5):1401-12
[94] Pepper MS. Transforming growth factor-beta: vasculogenesis,angiogenesis, and vessel wall integrity. Cytokine Growth Factor Rev, 1997,8(1) :21-43
[95] Robertson AK, Rudling M, Zhou X, et al. Disruption of TGF-beta signaling in T cells accelerates atherosclerosis. J Clin Invest,2003, 112(9):1342-50
[96] Sanford LP, Ormsby I, Gittenberger-de Groot AC, et al. TGFbeta2 knockout mice have multiple developmental defects that are non-overlapping with other TGFbeta knockout phenotypes.Development, 1997,124(13):2659-70
[97] Oh SP, Seki T, Goss KA, Imamura T, Yi Y, Donahoe PK, Li L, Miyazono K, ten Dijke P, Kim S, Li E. Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis. Proc Natl Acad Sci U S A,2000 ,97(6): 2626-31
[98] Galvin KM, Donovan MJ, et al.A role for smad6 in development and homeostasis of the cardiovascular system.Nat Genet,2000, 24(2):171-179
[99] Sohn M, Tan Y, Klein RL, Jaffa AA. Evidence for low-density lipoprotein-induced expression of connective tissue growth factor in mesangial cells.Kidney Int,2005,67(4):1286-1296
[100]Chen YL,Wu HW,Jiang MJ,Transforming growth factor-betal gene and proteinexpression associated with atherogenesis of cholesterol-fed rabbits.Histol Histop-athol,2000,15(2):421-428
[101]Kanamasa K,Otani N,et al.Suppression of cell proliferation by tissue plasminogen activator during the early phase after balloon injury minimizes intimal hyperplasia in hypercholesterolemic rabbits.Cardiovasc Pharmacol,2001,37(2):155-62
[102]Ettore Porreca,Concetta Di Febbo,et al.Increased transforming growth factor-beta(1) circulating levels and production in human monocytes after3-hydroxy-3-methyl-glutaryl-coenzyme a reductase inhibition with pravastatin.Am Coll Cardiol,2002,39(11):1752-57
[103]Muhlfeld AS,Spencer MW,et al.Hyperlipidemia aggravates renal disease in B6.ROP Os/+ mice.Kidney Int,2004,66(4):1393-1402
[104]Kim SI,Han DC,Lee HB.Lovastatin inhibits transforming growth factor-betal expression in diabetic rat glomeruli and cultured rat mesangial cells,J Am Soc Nephrol,2000,11(1):80-7
[105]司晓芸,贾汝汉,黄从新,等.宽叶缬草对高胆固醇血症大鼠肾组织内TGFβ1表达的影响.中国中药杂志,2003,28(9):845-848
[1]Hueber A,Wiedemann P,Esser P,Heimann K.Basic fibroblast growth factor mRNA,bFGF peptide and FGF receptor in epiretinal membranes of intraocular proliferative disorders(PVR and PDR).Int Ophthalmol,1996-97,20(6):345-50
[2]Sivalingam A,Kenney J,Brown GC,Benson WE,Donoso L.Busic fibroblast growth factor levels in the vitreous of patients with proliferative diabetic retinopathy.Arch Ophthalmol,1990,108(6):869-72
[3]Hanneken A,de Juan E Jr,Lutty GA,et al.Altered distribution of basic fibroblast growth factor in diabetic retinopathy.Arch Ophthalmol,1991,109(7):1005-11
[4]Gaudric A,N'guyen T,Moenner M,et al.Quantification of angiogenesis due to basic fibroblast growth factor in a modified rabbit corneal model.Ophthalmic Res,1992,24(3):181-8
[5]董宇,隋东明,赵秀珍.吴家祥血管内皮生长因子及碱性成纤维细胞生长因子与糖尿病大鼠视网膜早期血管病变的关系。中华医学杂志,2003,83(11):996-99
[6]Papetti M,Shujath J,Riley KN,Herman IM.FGF-2 antagonizes the TGF-betal-mediated induction of pericyte alpha-smooth muscle actin expression:a role for myf-5 and Smad-mediated signaling pathways.Invest Ophthalmol Vis Sci,2003,44(11):4994-5005
[7]Christinger HW,Muller YA,BerLeau LT,et al.Crystallization of the receptor binding domain of vascular endothelial growth factor.Proteins,1996,26(3):353-7
[8]Aiello LP,Bursell SE,Clermont A,et al.Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta-isoform-selective inhibitor.Diabetes,1997,46(9):1473-80
[9]Amin RH,Frank RN,Kennedy A,Eliott D,Puklin JE,Abrams GW.Vascular endothelial growth factor is present in glial cells of the retina and optic nerve of human subjects with nonproliferative diabetic retinopathy,Invest Ophthalmol Vis Sci,1997,38(1):36-47
[10]Spirin KS,Saghizadeh M,Lewin SL,et al.Basement membrane and growth factor gene expression in normal and diabetic human retinas.Curr Eve Res,1999,18(6):190-9
[11]Adamis AP,Miller JW,Bernal MT,et al.Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy.Am J Ophthalmol,1994,118(4):445-50
[12]Malik RA,Li C,Aziz W,Olson JA,et al.Elevated plasma CD105 and vitreous VEGF levels in diabetic retinopathy.J Cell Mol Med,2005,9(3):692-7
[13]Qaum T,Xu Q,Joussen AM,et al.VEGF-initiated blood-retinal barrier breakdown in early diabetes.Invest Ophthalmol Vis Sci,2001,42(10):2408-13
[14]Perrin RM,Konopatskaya O,Qiu Y,Harper S,Bates DO,Churchill AJ.Diabetic retinopathy is associated with a switch in splicing from anti- to pro-angiogenic isoforms of vascular endothelial growth factor.Diabetologia,2005,48(11):2422-7
[15]Thieme H,Aiello LP,Takagi H,Ferrara N,King GL.Comparative analysis of vascular endothelial growth factor receptors on retinal and aortic vascular endothelial cells.Diabetes,1995,44(1):98-103
[16]Ambati J,Chalam KV,Chawla DK,et al.Elevated gamma-aminobutyric acid,glutamate,and vascular endothelial growth factor levels in the vitreous of patients with proliferative diabetic retinopathy.Arch Ophthalmol,1997,115(9):1161-6
[17]Ozaki H,Seo MS,Ozaki K,et al.Blockade of vascular endothelial cell growth factor receptor signaling is sufficient to completely prevent retinal neovascularization.Am J Pathol,2000,156(2):697-707
[18]Pfeiffer A,Middelberg-Bisping K,Drewes C,Schatz H..Elevated plasma levels of transforming growth factor-beta 1 in NIDDM.Diabetes Care,1996,19(10):1113-7
[19]Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease:the Scandinavian Simvastatin Survival Study(4S).Lancet,1994,344(8934):1383-9
[20]Monique M,Pascal JV,et al.Glucose-mediated regulation of transforming growth factor-beta(TGF-β) and TGF-β receptor in human retinal endothial cells. Current Eye Res, 1999, 19(2):162-170
[21] Raul AP,Janice AJ, Bert MG. Effects of TGF-pandTGF-β neutralizing antibodies on the fibroblast-induced collagen gel contraction:implications for proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci, 1994,35(7):2804-2809
[22] Eisenstein R, GrantBD. Growth inhibitory activities in a vascular tissues arerecognized by antitransforming growth factor β antibodies.CurrEye Res, 1991, 10(2):157-162
[23] Grant MB, Caballero S, Bush DM, Spoerri PE. Fibronectin fragments modulate human retinal capillary cell proliferation and migration.Diabetes,1998, 47(8):1335-40
[24] Spirin KS, Saghizaden M, Lewin SL, etal. Basement membrane and growth factorgene expression in normal and diabetic human retinal.Curr Eye Res, 1999, 18(6):490-499.
[25] Hosoda Y, Okada M, Matsumura M, et al, Intravitreal neo-vascular tissue of proliferative diabetic retinopathy:an immunohistochemical study. Ophthalmic Res, 1992, 24 (5):260-264
[26] Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature, 2003, 425(6958):577-84
[27] Esser P, Bartz-Schmidt KU, Walter P, Kaszli F, Heimann K, Weller M. Apoptotic cell death in proliferative vitreoretinopathy.Ger J Ophthalmol, 1996, 5(2):73-8
[28] El Ghrably I, Powe DG, Orr G, Fischer D, et al. Apoptosis in proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci.2004,45(5):1473-9
[29] Meyer-Schwickerath R, Pfeiffer A, et al. Vitreous levels of the insulin-like growth factors I and II, and the insulin-like growth factor binding proteins 2 and 3, increase in neovascular eye disease. Studies in nondiabetic and diabetic subjects. J Clin Invest., 1993, 92(6):2620-5
[30] Grant MB, Mames RN, Fitzgerald C, Ellis EA, Aboufriekha M, Guy J.Insulin-like growth factor I acts as an angiogenic agent in rabbit cornea and retina:comparative studies with basic fibroblast growth factor.Diabetologia,1993,36(4):282-91
[31]Layton CJ,Becket S,Osborne NN.The effect of insulin and glucose levels on retinal glial cell activation and pigment epithelium-derived fibroblast growth factor-2.Mol Vis,2006,12:43-54
[31]Danis RP,Bingaman DP.insulin-like growth factor-1 retinal microangiopathy in the pig eye.Ophthalmology,1997,104(10):1661-9
[32]Loukovaara S,Immonen IJ,Koistinen R,Rutanen EM,Hiilesmaa V,Loukovaara M,Kaaja RJ.The insulin-like growth factor system and Type 1 diabetic retinopathy during pregnancy.J Diabetes Complications,2005,19(5):297-304
[33]Spoerri PE,Afzal A,Li Calzi S,Shaw LC,Cai J,Pan H,Boulton M,Grant MB.Effects of VEGFR-1,VEGFR-2,and IGF-IR hammerhead ribozymes on glucose-mediated tight junction expression in cultured human retinal endothelial cells.Mol Vis,2006,12:32-42
[34]Averbukh E,Weiss O,Halpert M,Yanko R,Moshe R,Nephesh I,Flyvbjerg A,Yanko L,Raz I.Gene expression of insulin-like growth factor-Ⅰ,its receptor and binding proteins in retina under hypoxic conditions.Metabolism,1998,47(11):1331-6
[35]Sharp PS.The role of growth factors in the development of diabetic retinopathy.Metabolism,1995,44(10 Suppl 4):72-5
[36]Bergman PB,Moravski CJ,Edmondson SR,et al.Expression of the IGF system in normal and diabetic transgenic(mRen-2)27 rat eye.Invest Ophthalmol Vis Sci,2005,46(8):2708-15
[37]Ruberte J,Ayuso E,Navarro M,et al.Increased ocular levels of GF-1 in transgenic mice lead to diabetes-like eye disease.J Clin Invest,2004,113(8):1149-57
[38]Poulaki V,Joussen AM,Mitsiades N,et al.Insulin-like growth factor-Ⅰ plays a pathogenetic role in diabetic retinopathy.Am J Pathol,2004,165(2):457-69
[39]Pastor JC.Proliferative vitreoretinopathy:an overview.Surv Ophthalmol.1998,13(1):3-18
[40] Limb GA, Chignell AH, Green W, et al. Distribution of TNF alpha and its reactive vascular adhesion molecules in fibrovascular membranes of proliferative diabetic retinopathy. Br J Ophthalmol,1996,80(2): 168-73
[41] Demircan N, Safran BG, Soylu M, et al. Determination of vitreous interleukin-1 (IL—1) and tumour necrosis factor (TNF) levels in proliferative diabetic retinopathy. Eye. 2005,11
[42] Doganay S, Evereklioglu C, Er H, et al. Comparison of serum NO, TNF-alpha, IL-lbeta, sIL-2R, IL-6 and IL-8 levels with grades of retinopathy in patients with diabetes mellitus. Eye, 2002, 16(2):163-70
[43] Takashi Y, Tsugiyasu K,Yasutakak, etal. Inflammatory cytokines in vitreous fluid and serum of patients with diabetic vituro retinopathy. J Dibetes Compications, 2001, 15(5):257-259
[44] Hussain MJ, Peakman M,MallatiH. etal.Elevated serum levels of macrophage derived cytokines precede and accompany the onset on IDDM[J].Diabetologia 1999, 39(1):60-69
[45] Ben-Mahmud BM, Mann GE, Datti A, et al. Tumor necrosis factor-alpha in diabetic plasma increases the activity of core 2 GlcNAc-T and adherence of human leukocytes to retinal endothelial cells:significance of core 2 GlcNAc-T in diabetic retinopathy.Diabetes, 2004, 53(11):2968-76
[46] Joussen AM, Poulaki V, Mitsiades N, et al. Nonsteroidal anti-inflammatory drugs prevent early diabetic retinopathy via TNF-alpha suppression. FASEB J, 2002,16(3):438-40
[47] Funatsu H, YamashitaH, Sakata K, et al. Vitreous levels of vascular endothelial growth factor and intercellular adhesion molecule 1 are related to diabetic macular edema. Ophthalmology, 2005 ,112(5):806-16
[48] Limb GA, Chignell AH, Cole CJ, et al. Intercellular adhesion molecule-1 in proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci, 1997 ,38(5): 1043-8
[49] Chen W, Esselman WJ, Jump DB, Busik JV. Anti-inflammatory effect of docosahexaenoic acid on cytokine-induced adhesion molecule expression in human retinal vascular endothelial cells,lnvest Ophthalmol Vis Sci,2005,46(11):4342-7
[50]Yoshizawa M,Nagai Y,Ohsawa K,et al.Elevated serum levels of soluble vascular cell adhesion molecule-1 in NIDDM patients with proliferative diabetic retinopathy.Diabetes Res Clin Pract,1998,42(1):65-70
[51]Boulbou MS,Koukoulis GN,Petinaki EA,et al.Soluble adhesion molecules are not involved in the development of retinopathy in type 2 diabetic patients.Acta Diabetol,2004,41(3):118-22
[52]Chert W,Jump DB,Grant MB,Esselman WJ,Busik JV.Dyslipidemia,but not hyperglycemia,induces inflammatory adhesion molecules in human retinal vascular endothelial cells,Invest Ophthalmol Vis Sci,2003,;44(11):5016-22
[53]王国平,邓仲端,瞿智玲.氧化低密度和极低密度脂蛋白对单核细胞血小板衍生生长因子B链表达的影响[J].中国动脉硬化杂志,1995,3(3):221-223
[54]尹鸿操,刘佩毛.mm2LDL对内皮细胞转录因子NF2JB活性的影响[J].中国医学科学院学报,2001,23(4):312-316.
[55]Wiedemann P.Growth factors in retinal diseases:proliferative vitreoretinopathy,proliferative diabetic retinopathy,and retinal degeneration.Surv Ophthalmol,1992,36(5):373-84
[56]Cox OT,Simpson DA,Stitt AW,Gardiner TA.Sources of PDGF expression in murine retina and the effect of short-term diabetes.Mol Vis,2003,9:665-72
[57]Zhang SX,Wang JJ,Gao G,et al.Pigment epithelium-derived factor (PEDF) is an endogenous antiinflammatory factor.FASEB J,2006,20(2):323-5
[58]Yamagishi S,Inagaki Y,Nakamura K,Abe R,Shimizu T,Yoshimura A,Imaizumi T.Pigment epithelium-derived factor inhibits TNF-alpha-induced interleukin-6 expression in endothelial cells by suppressing NADPH oxidase-mediated reactive oxygen species generation.J Mol Cell Cardiol,2004,37(2):497-506
[59]Hammes HP,Lin J,Rennet O,Shani M,Lundqvist A,Betsholtz C,Brownlee M,Deutsch U.Pericytes and the pathogenesis of diabetic retinopathy.Diabetes,2002,51(10):3107-12
[60]刘丽娟,李茂欣,汤旭磊,高林,朱任之.糖尿病大鼠视网膜早期病变中PDGF-B的表达.第四军医大学学报,2005,26(23):2159-2161
[61]Munjal ID,McLean NV,Grant MB,Blake DA.Differences in the synthesis of secreted proteins in human retinal endothelial cells of diabetic and nondiabetic origin.Curr Eye Res,1994,13(4):303-10
[62]Patel B,Hiscott P,Charteris D,et al.Retinal and preretinal localisation of epidermal growth factor,transforming growth factor alpha,and their receptor in proliferative diabetic retinopathy.Br J Ophthalmol,1994,78(9):714-8
[63]Sato Y,Okamura K,Morimoto A,Hamanaka R,Hamaguchi K,Shimada T,Ono M,Kohno K,Sakata T,Kuwano M.Indispensable role of tissue-type plasminogen activator in growth factor-dependent tube formation of human microvascular endothelial cells in vitro.Exp Cell Res,1993,204(2):223-9
[2] Sivitz WI. Lipotoxicity and glucotoxicity in type 2 diabetes.Effects on development and progression. Postgrad Med, 2001 ,109(4):55-9, 63-4
[3] Biljana M, Robert JG, David MN,JoAnn EManson,et al .A Prospective Study of Serum Lipids and Risk of Diabetic Macular Edema in Type 1 Diabetes. Diabetes, 2004,53: 2883-2892
[4] Timothy JL, Alicia JJ, Deyi Z, et al.Diabetic retinopathy and serum lipoprotein subclasses in the DCCT/EDIC cohort.IVOS, 2004,45(3):910-18
[5] Leung H, Wang JJ, Rochtchina E, Wong TY,et al Dyslipidaemia and Microvascular disease in the retina . Eye, 2005, 19, 861-868
[6] Larsson LI, Alm A, Lithner F, Dahlen G, Bergstrom R. The association of hyperlipidemia with retinopathy in diabetic patients aged 15-50 years in the county of Umea. Acta Ophthalmol Scand, 1999 ,77(5):585-91
[7] Cusick M,Chew EY,et al. Histopathology and regression of retinal hard exudat.es in diabetic retinopathy after reduction of elevated serum lipid levels. Phthalmology, 2003, 110(11):2126 33
[8] Mandarino U, Finlayson J, Hassell JR. High glucose down regulates glucose transport activity in retinal capillary pericytes but not endothelial cells. Invest Ophthalmol Vis Res, 1994,35(8):964-972
[9] Podesta F, Romeo G, Liu WH, et al. Bax is increased in the retina of diabetic subjects and is associated with pericyte apoptosis in vivo and in vitro.Am J Pathol, 2000, 156(3):1025-32
[10] Li W, Yanoff M, Liu X, Ye X. Retinal capillary pericyte apoptosis in early human diabetic retinopathy.Chin Med J (Engl), 1997, 110(9):659-63
[11]Mizutani M,Kern TS,Lorenzi M.Accelerated death of retinal microvascular cells in human and experimental diabetic retinopathy.J Clin Invest,1996,97(12):2883-90
[12]刘学政,萧鸿,曲维新,等.糖尿病大鼠视网膜毛细血管细胞凋亡及其凋亡相关基因的表达.中华眼科杂志,2001,37(1):59-62
[13]Beltramo Z,Berrone E,Buttiglieris,Porta M.Thiamine and benfotiamineprevent increased apoptosis in endothelial cells and pericytes cultured in high glucose.Diabetes Metab Res Rev,2004,20(4):330-336
[14]Jump DB.Dietary polyunsaturated fatty acids and regulation of gene transcription.Curr Opin Lipidol.2002,13(2):155-164
[15]Jump DB.TThe biochemistry of n-3 polyunsaturated fatty acids.J Biol Chem.2002,277(11):8755-8
[16]胡俊斌,魏文宁,丁桂芝,等.糖尿病患者凝血与纤溶状态初探.中华内分泌代谢杂志,1996,12:118-119
[17]wiedfmann P.Growth factors in retinal diseases:proliferative vitreoretinopathy,proliferative diabetic retinopathy and retinal degeneration.Surv Ophthalmol,1992,36(5):373-384
[18]Pfeiffer A,Middelberg-Bisping K,Drewes C,Schatz H..Elevated plasma levels of transforming growth factor-beta 1 in NIDDM.Diabetes Care,1996,19(10):1113-7
[19]Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease:the Scandinavian Simvastatin Survival Study(4S).Lancet,1994,344(8934):1383-9
[20]Derynck R,Zhang YE.Smad-dependent and Smad-independent pathways in TGF-beta family signalling.Nature,2003,425(6958):577-84
[21]Esser P,Bartz-Schmidt KU,Walter P,Kaszli F,Heimann K,Weller M.Apoptotic cell death in proliferative vitreoretinopathy.Ger J Ophthalmol,1996,5(2):73-8
[22]El Ghrably I,Powe DG,Orr G,Fischer D,et al.Apoptosis in proliferative vitreoretinopathy.Invest Ophthalmol Vis Sci.2004,45(5):1473-9
[23]Spirin KS,Saghizaden M,Lewin SL,etal.Basement membrane and growth factor gene expression in normal and diabetic human retinal.Curr Eye Res,1999,18(6):490-499.
[24]Hosoda Y,Okada M,Matsumura M,et al,Intravitreal neo-vascular tissue of proliferative diabetic retinopathy:an immunohistochemical study.Ophthalmic Res,1992,24(5):260-264
[25]Porreca E,Di Febbo C,Baccante G,et al.Increased transforming growth factor-beta(1) circulating levels and production in human monocytes after 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase inhibition with pravastatin.J Am Coll Cardiol,2002,39(11):1752-7
[26]Muhlfeld AS,Spencer MW,Hudkins KL,Kirk E,LeBoeuf RC,Alpers CE.Hyperlipidemia aggravates renal disease in B6.ROP Os/+ mice.Kidney Int.2004,66(4):1393-402
[27]Ryu JK,Han JY,Chu YC,et at.Expression of cavernous transforming growth factor-betal and its type Ⅱ receptor in patients with erectile dysfunction.Int J Androl,2004,27(1):42-9
[28]Natarajan R,Gerrity RG,Gu JL,Lanting L,Thomas L,Nadler JL.Role of 12-lipoxygenase and oxidant stress in hyperglycaemia-induced acceleration of atherosclerosis in a diabetic pig model.Diabetologia,2002,45(1):125-33
[29]Sen K,Misra A,Kumar A,Pandey RM,Simvastatin retards progression of retinopathy in diabetic patients with hypercholesterolemia.Diabetes Res Clin Pract,2002,56(1):1-11
[30]Hirase K,IkedaT,Sotozono C,etal.Transforming growth factor-β2 in the vitreous in proliferative diabetic retinopathy.ArchOphthalmol,1998,116(6):738-741
[31]沈炜,柳林,满晓波,刘志勇,李慎菁.实时荧光聚合酶链反应定量检测大鼠视网膜中转化生长因子β1和β2的表达.中华眼底病杂志,2005,21(1):48-49
[32]Obata H,Kaburaki T,Kato M,Yamashita H.Expression TGF-beta type Ⅰand typeⅡreceptors in rat eyes.Curr Eye Res,1996,15(3):335-340
[33]Ochiai Y,Ochiai H.Higher concentration of transforming growth factor-beta in aqueous humor of gIaucomatous eyes and diabetic eyes.JPN Ophthalmol,2002,46(3):249-253
[34]Matsumoto Y,Takahashi M,Ogata M.Relationship between glycoxidation and cytokines in the vitreous of eyes with diabetic retinopathy.JPN Ophthalmol,2002,46(4):406-412
[35]Bochaton-Piallat ML,Kapetanios AD,Donati G,et al.TGF-betal,TGF-beta receptor Ⅱ and ED-A fibronectin expression in myofibroblast of vitreoretinopathy.Invest Ophthalmol Vis Sci,2000,41(8):2336-42
[36]Spirin KS,Saghizaden M,Lewin SL,etal.Basement membrane and growth factor gene expression in normal and diabetic human retinal.Curr Eye Res,1999,18(6):490-499
[37]Hosoda Y,Okada M,Matsumura M,et al.Intravitreal neo-vascular tissue of proliferative diabetic retinopathy:an immuno-histoche-mical study.Ophthalmic Res,1992,24(5):260-264
[38]Klein BE,Moss SE,Klein R,et al.The Wisconsin epidemioiogic study of diabetic retinopathy.Relationship of serum cholesterol to retinopethy and bard exudates.Ophthalmology,1991,98(8):1261-65
[39]张胜兰,等.糖尿病患者红细胞变形能力受损.中华内分泌代谢志,1989,5(2):95-96
[40]Eisenstein R,Grant BD.Growth inhibitory activities in a vascular tissues are recognized by anti transforming growth factor β antibodies.Curr Eye Res,1991,10(2):157-162
[41]Hollbom M,Kohen L,Wiedemann P,Enzmann V.The influence of proinflammatory cytokines on human retinal pigment epithelium cell receptors.Graefes Arch Clin Exp Ophthalmology,2001,239(4):294-301
[42]Monique M,Pascal JV,et al.Glucose-mediated regulation of transfo-rming growth factor-beta(TGF-β) and TGF-βreceptor in human retinal endothial cells.Current Eye Res,1999,19(2):162-170
[43]郭长梅,惠延年,马吉献,等.转化生长因子β受体Ⅱ在增生性玻璃体视网膜病变增生膜中的表达.眼科学报,2003,19(4):244-247.
[44]Bert MG,Patrcia AD,Ronald G,et al.Demonstration of vasoproliferative activity from mammalian retina.Cell Biology,1980,84: 298-304
[145]夏欣,许迅,顾青.牛视网膜微血管内皮细胞和周细胞的体外培养.中华眼底病杂志,2004,20(1):23-26
[46]席兴华,姜德咏,唐罗生.牛视网膜微血管周细胞和内皮细胞的选择性培养.眼科研究,2000,18(6):493-496
[47]Cohen RA,Hennekens CH,Christen WG,et al.Determinants of retinopathy progression in type 1 diabetes mellitus.Am Med,1999,107(1):45-51
[48]Li W,Liu X,et,al.Cultured retinal capillary pericytes die by apoptosis after an abrupt fluctuation from hyperglycemic levels:a comparative study with retinal capillary endothelial cells.Diabetologia,1996,39:537-541
[49]Schonfelder U,Hofer A,Paul M,Funk RH.In situ observation of living pericytes in rat retinal capillaries.Microvasc Res,1998,56(1):22-9.
[50]Song W,Barth JL,Lu K,et al.Effects of modified low-density lipoproteins on human retinal pericyte survival.Ann N Y Acad Sci.2005,1043:390-5.
[51]Sellmayer A,Hrboticky N,Weber PC.Lipids in vascular function.Lipids,1999,34(suppl):S13 -S18.
[52]Berliner JA,Heinecke JW.The role of oxidized lipoproteins in atherogenesis.Free Raddic Biol Med,1996,20(5):707-708
[53]Yokoyama M,Hirata KI,Miyake R,et al.LysophoPhatidylcholine:Essential role in the inhibition of endothelium dependent vasorelaxation by oxidized low density lipoprotein.Biochem Biophy Resea Commun,1990,168(1):301-303
[54]Schaefer CA,Kuhlmann CR,Gast C,et al.Statins prevent oxidized low-density lipoprotein- and lysophosphatidylcholine-induced proliferation of human endothelial cells.Vascul Pharmacol.2004,41(2):67-73
[55]Dulak J,Jozkowicz A,Dichtl W,et al.Vascular endothelial growth factor synthesis in vascular smooth muscle cells is enhanced by 7 ketocholesterol and lysophosphatidylcholine independently of their effect on nitric oxide generation.Atherosclerosis,2001,159(2):325-32
[56]Sata M,Walsh K.Endothelial cell apoptosis induced by oxidized LDL is associated with the down-regulation of the cellular caspase inhibitor FLIP.J Biol Chem,1998,273(50):33103-33106
[57]Heiloth A,Heermeier K,et al.Stimulation of NADPH oxidase by oxidized low-density lipoprotein induces proliferation of human vascular endothelial cells.Am Soc Nephrol,2000,11(10):1819-1825
[58]Rymaszewski Z,Szymanski PT,et al.Human retinal Vascular cells differ from umbilical cells in synthetic functions and their response to glucose.PSEBM,1992,199(2):183-191
[59]马建芳,杨中汉,宋志宏,等.大利量葡萄糖诱导人视网膜内皮细胞凋亡.第一军医大学学报,2003,23(5):435-438
[60]Bucala R.Mitchell R.Arnold K.et al.Identification of the major site of apolipoprotein B modification by advanced glycosylation end products blocking uptakeby the low density lipoprotein receptor.J Biol Chem,1995,270(18):10828-10832
[61]Jump DB.The biochemistry of n-3 polyunsaturated fatty acids.J Biol Chem,2002,277(11):8755-8
[62]Lauritzen T,Frost-Larsen K,et al.Effect of one year of near-normal blood glues levels on retinopathy in insulin-dependent diabetics.Lancet,1983,1:2000-2004
[63]Kenne WF,The role of lipids in renal disease:future challenges.Kidney Int,2000:57(Suppl):S27-31
[64]Tedgui A,Mallat Z.Anti-inflammatory mechanisms in the vascular wall.Circ Res,2001,88(9):877-87
[65]Pintavorn P,Ballermann BJ.TGF-beta and the endothelium during immune injury.Kidney Int,1997,51(5):1401-12
[66]Pepper MS.Transforming growth factor-beta:vasculogenesis,angiogenesis,and vessel wall integrity.Cytokine Growth Factor Rev.1997,8(1):21-43
[67]Robertson AK,Rudling M,Zhou X,et al.Disruption of TGF-beta signaling in T cells accelerates atherosclerosis.J Clin Invest, 2003,112(9):1342-50
[68]Sanford LP,Ormsby I,Gittenberger-de Groot AC,et al.TGFbeta2knockout mice have multiple developmental defects that are non-overlapping with other TGF beta knockout phenotypes.Development,1997,124(13):2659-70
[69]Oh SP,Seki T,Goss KA,Imamura T,et al.Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis.Proc Natl Acad Sci U S A.2000,97(6):2626-31
[70]Galvin KM,Donovan MJ,Lynch CA,et al.A role for smad6 in development and homeostasis of the cardiovascular system.Nat Genet,2000,24(2):171-4
[71]Sohn M,Tan Y,Klein RL,Jaffa AA.Evidence for low-density lipoprotein-induced expression of connective tissue growth factor in mesangial cells.Kidney Int,2005,67(4):1286-1296
[72]Lassila M,Seah KK,Allen TJ,et al.Accelerated nephropathy in diabetic apolipoprotein e-knockout mouse:role of advanced glycation end products.J Am Soc Nephrol.2004,15(8):2125-38
[73]Muhlfeld AS,Spencer MW,Hudkins KL,Kirk E,LeBoeuf RC,Alpers CE.Hyperlipidemia aggravates renal disease in B6.ROP Os/+ mice.Kidney Int,2004,66(4):1393-402
[74]Chen YL,Wu HW,Jiang MJ.Transforming growth factor-betal gene and protein expression associated with atherogenesis of cholesterol-fed rabbits.Histol Histopathol,2000,15(2):421-8
[75]RayChaudhury A,D'Amore PA.Endothelial cell regulation by transforming growth factor-beta.J Cell Biochem.1991,47(3):224-9
[76]Leksa V,Godar S,Schiller HB,Fuertbauer E,et al.TGF-beta-induced apoptosis in endothelial cells mediated by M6P/IGFII-R and mini-plasminogen.Cell Sci,2005,118(19):4577-86
[77]Antonelli Orlidge A,Saunders KB,Smith SR,D'Amore PA.An activated form of transforming growth factor beta is preduced by cocultures of endothelial cells and pericytes.Proc Natl Acad Sci U S A,1989,86(12):4544-8
[78] Wakefield LM, Smith DM, Flanders KC, Sporn MB. Latent transforming growth factor-beta from human platelets. A high molecular weight complex containing precursor sequences. J Biol Chem, 1988,263(16) :7646-54
[79] Lyons RM, Keski-Oja J, Moses HL. Proteolytic activation of latent transforming growth factor-beta from fibroblast-conditioned medium. J Cell Biol, 1988, 106(5):1659-65
[80] Flaumenhaft R,Abe M, Mignatti P, et al. Basic fibroblast growth factor-induced activation of transforming growth factor beta in endothelial cell regulation of plasminogen activator activity.J Cell Biol, 1992, 118(4):901-9
[81] Knott RM, Muckersie E, Robertson M, Forrester JV. Glucose-dependent regulation of DNA synthesis in bovine retinal endothelial cells.Curr Eye Res, 1998 ,17(1):1-8
[82] Ishida K, Yamashita H, Katagiri H, Oka Y. Regulation of glucose transporter 1 (GLUT1) gene expression by epidermal growth factor in bovine corneal endothelial cells. Jpn J Ophthalmol.1995, 39(3): 225-32
[83] Sohn M, Tan Y, Wang B, Klein RL, et al. Mechanisms of low-density 1 ipoprotein-induced expression of connective tissue growth factor in human aortic endothelial cells. Am J Physiol Heart Circ Physiol,2006 ,290(4):H1624-34
[84] Saura M, Zaragoza C, Herranz B, et al. Nitric oxide regulates transforming growth factor-beta signaling in endothelial cells.Circ Res, 2005,97(11):1115-23
[85] Hu T, Ramachandrarao SP, Siva S, et al.Reactive oxygen species production via NADPH oxidase mediates TGF-beta-induced cytoskeletal alterations in endothelial cells. Am Physiol Renal Physiol,2005, 289(4):816-825
[86] NorataGD, Callegari E, Marchesi M, et al. High-density lipoproteins induce transforming growth factor-beta2 expression in endothelial cells. Circulation, 2005, 111(21) :2805-281i
[87] Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling.Nature,2003,425(6958):577-84
[88]Raul AP,Janice AJ,Bert MG.Effects of TGF-βandTGF-βneutralizing antibodies on the fibroblast-induced collagen gel contraction:implications for proliferative vitreoretinopathy.Invest Ophthalmol Vis Sci,1994,35(7):2804-2809
[1]McGarry JD.Banting lecture 2001:dysregulation of fatty acid metabolism in the etiology of type 2 diabetes.Diabetes,2002,51(1):7-18
[2]Sivitz WI.Lipotoxicity and glucotoxicity in type 2 diabetes.Effects on development and progression.Postgrad Med,2001,109(4):55-9,63-4
[3]Chowdhury TA,Hopkins D,Dodson PM,Vafidis GC.The role of serum lipids in exudative diabetic maculopathy:is there a place for lipid lowering therapy?Eye,2002,6(6):689-93
[4]Ravid M,Brosh D,Ravid-Safran D,Levy Z,Rachmani R.Main risk factors for nephropathy in type 2 diabetes mellitus are plasma cholesterol levels,mean blood pressure,and hyperglycemia.Arch Intern Med,1998,158(9):998-1004
[5]Hadjadj S,Pean F,Gallois Y,et al.Different patterns of insulin resistance in relatives of type 1 diabetic patients with retinopathy or nephropathy:the Genesis France-Belgium Study.Diabetes Care,2004,27(11):2661-68
[6]Coppack SW,Evans RD,Fisher RM,et al.Adipose tissue metabolism in obesity:lipase action in vivo before and after a mixed meal.Metabolism,1992,41(3):264-72
[7]Weinstock PH,Levak-Frank S,Hudgins LC,Radner H,Friedman JM,Zechner R,Breslow JL.Lipoprotein lipase controls fatty acid entry into adipose tissue,but fat mass is preserved by endogenous synthesis in mice deficient in adipose tissue lipoprotein lipase.Proc Natl Acad Sci U S A,1997,94(19):10261-6
[8]Goldberg RB.Lipid disorders in diabetes.Diabetes Care,1981,4(5):561-72.
[9]Goldberg RB,Capuzzi D.Lipid disorders in type 1 and type 2 diabetes.Clin Lab Med,2001,21(1):147-72
[10]Goldberg IJ.Clinical review 124:Diabetic dyslipidemia:causes and consequences.J Clin Endocrinol Metab,2001,86(3):965-71
[11]Poisson JP.Essential fatty acid metabolism in diabetes.Nutrition,1989,5(4):263-6
[12]Rossetti L,Goldberg IJ.A new piece in the diabetes puzzle.Nat Med,2002,8(2):112-4
[13]Vessby B.Dietary fat and insulin action in humans.Br Nutr,2000,83(suppl 1):S91-S96
[14]Zenobi PD,Holzmann P,Glatz Y,Riesen WF,Froesch ER.Improvement of lipid profile in type 2(non-insulin-dependent) diabetes mellitus by insulin-like growth factor I. Diabetologia,1993,36(5):465-9
[15] McGarry JD. What if Minkowski had been ageusic? An alternative angle on diabetes. Science, 1992,258(5083):766-70
[16] Larsson LI, Alm A, Lithner F, Dahlen G, Bergstrom R. The association of hyperlipidemia with retinopathy in diabetic patients aged 15-50 years in the county of Umea.Acta Ophthalmol Scand ,1999,77(5):585-591
[17] Natarajan R, Gerrity RG, Gu JL, Lanting L, Thomas L, Nadler JL. Role of 12-lipoxygenase and oxidant stress in hyperglycaemia-induced acceleration of atherosclerosis in a diabetic pig model, Diabetologia. 2002 Jan;45(1):125-33.
[18] Sen K, Misra A, Kumar A, Pandey RM. Simvastatin retards progression of retinopathy in diabetic patients with hypercholesterolemia,Diabetes Res Clin Pract, 2002, 56 (1) : 1-11
[19] Cusick M, Chew EY, et al. Histopathology and regression of retinal hard exudates in diabetic retinopathy after reduction of elevated serum lipid leveis. Phthalmology, 2003, 110(11):2126-2133
[20] Gupta A, Gupta V, Thapar S, Bhansali A. Lipid-lowering drug atorvastatin as an adjunct in the management of diabetic macular edema. Am Ophthalmol, 2004 ,137(4):675-82
[21] Klein R, Marino EK, Kuller LH, Polak JF, Tracy RP, Gottdiener JS, Burke GL, Hubbard LD, Boineau R. The relation of atherosclerotic cardiovascular disease to retinopathy in people with diabetes in the Cardiovascular Health Study.Br J Ophthalmol, 2002 ,86(1):84-90.
[22] Ferris FL 3rd, Chew EY, Hoogwerf BJ. Serum lipids and diabetic retinopathy. Early Treatment Diabetic Retinopathy Study Research Group.Diabetes Care, 1996,19(11):1291-3
[23] Chew EY, Klein ML, Ferris FL 3rd, Remaley NA, Murphy RP, Chantry K, Hoogwerf BJ, Miller D. Associat ion of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy. Early Treatment Diabetic Retinopathy Study (ETDRS) Report 22. Arch Ophthalmol, 1996,114(9):1079-84
[24]van Leiden HA,Dekker JM,Moll AC,Nijpels G,Heine RJ,Bouter LM,Stehouwer CD,Polak BC.Risk factors for incident retinopathy in a diabetic and nondiabetic population:the Hoorn study.Arch Ophthalmol,2003,121(2):245-51
[25]Klein BE,Moss SE,Klein R,et al,The Wisconsin epidemiologic study of diabetic retinopathy.Relationship of serum cholesterol to retinopethy and hard exudates.Ophthalmology,1991,98(8):1261-65
[26]Fernandez-Robredo P,Moyn D,et al.Vitamins C and e reduce retinal oxidative stress and nitric oxide metabolites and prevent ultrastructural alterations in porcine hypercholesterolemia.Invest Ophthalmol Vis Sic,2005,46(4):1140-1146
[27]Leung H,Wang JJ,Rochtchina E,et al.Dyslipidaemia and microvascular disease in the retina.Eye,2005,19(8):861-868
[28]Yamakawa K,Bhutto IA,Lu Z,Watanabe Y,Amemiya T.Retinal vascular changes in rats with inherited hypercholesterolemia corrosion cast demonstration.Curr Eye Res,2001,22(4):258-65
[29]张胜兰,等.糖尿病患者红细胞变形能力受损.中华内分泌代谢杂志,1989,5(2):95-96
[30]Coulon J,Willems D,Dorchy H.Increase in C-reactive protein plasma levels during diabetes in infants and young adults.Presse Med,2005,34(2 Pt 1):89-93
[31]Chen W,Jump DB,et al.Dyslipidemia,but not hyperglycemia,induces inflammatory adhesion molecules in human retinal vascular endothelial cells.Invest Ophthalmol Vis Sci,2003,44(11):5016-22
[32]Miyamoto K,Ogura Y.Pathogenetic potential of leukocytes in diabetic retinopathy.Semin Ophthalmol,1999,14(4):233-9
[33]Miyamoto K,Khosrof S,Bursell SE,Rohan R,Murata T,Clermont AC,Aiello LP,Ogura Y,Adamis AP.Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition.Proc Natl Acad Sci U S A,1999,96(19):10836-41
[34]胡俊斌,魏文宁,丁桂芝,等.糖尿病患者凝血与纤溶状态初探.中华内分泌 代谢杂志,1996,12:118-119
[35]汪崇文,郑汉莲,石俊等.2型糖尿病脂质代谢紊乱与视网膜病变相互关系研究.中华医学杂志,2001,25(1):36-37
[36]Darland DC,Massingham LJ,et al.Pericyte production of cellassociated VEGF is differentiation-dependent and is associated with endothelial survival.Dev Biol,2003,264(1)275-288
[37]Cohen RA,Hennekens CH,Christen WG,et al.Determinants of retinopathy progression in type 1 diabetes mellitus.Am Med,1999,107(1):45-51
[38]Li W,Liu X,Yanoff M,Cohen S,Ye X.Cultured retinal capillary pericytes die by apoptosis after an abrupt Fluctuation from high to low glucose levels:a comparative study with retinal capillary endothelial cells.Diabetologia,1996,39(5):537-47
[39]Yatoh S,Mizutani M,et al.Antioxidants and an inhibitor of advanced glycation ameliorate death of retinal microvascular cells in diabetic retinopathy.Diabetes Metab Res Rev,2006,22(1):38-45
[40]Lecomte M,Denis U,Ruggiero D,et al.Involvement of caspase-10in advanced glycation end-product-induced apoptosis of bovine retinal pericytes in culture.Biochim Biophys Acta,2004,1689(3):202-11
[41]Dagher Z,Park YS,et al.Studies of rat and human retinas predict a role for the polyol pathway in human diabetic retinopathy.Diabetes,2004,53(9):2404-11
[42]Schonfelder U,hofer A,Paul M,Funk RH.In situ observation of living pericytes in rat retinal capillaries.Microvasc Res,1998,56(1):22-9.
[43]Podesta F,Romeo G,Liu WH,Krajewski S,Reed JC,Gerhardinger C,Lorenzi M.Bax is increased in the retina of diabetic subjects and is associated with pericyte apoptosis in vivo and in vitro.Am J Pathol,2000,156(3):1025-32
[44]Li W,Yanoff M,Liu X,Ye X.Retinal capillary pericyte apoptosis in early human diabetic retinopathy.Chin Med.I(Engl),1997,110 (9):659-63
[45]Song W,Barth JL,Lu K,Yu Y,Huanz Y,Gittinger CK,Argraves WS,Lyons TJ.Effects of modified low-density lipoproteins on human retinal pericyte survival.Ann N Y Acad Sci,2005,1043:390-5
[46]Lupo G,Anfuso CD,Ragusa N,et al.t-Butyl hydroperoxide and oxidized low density lipoprotein enhance phospholipid hydrolysis in lipopolysaccharide- stimulated retinal pericytes.Biochim Biophys Acta,2001,1531(1-2):143-155
[47]Mizutani M,Kern TS,Lorenzi M.Accelerated death of retinal microvascular cells in human and experimental diabetic retinopathy.J Clin Invest,1996,97(12):2883-90
[48]刘学政,萧鸿,曲维新,等.糖尿病大鼠视网膜毛细血管细胞凋亡及其凋亡相关基因的表达.中华眼科杂志,2001,1:59-62
[49]Beltramo Z,Berrone E,Buttiglieris,Porta M.Thiamine and benfotiamine prevent increased apoptosis in endothelial cells and pericytes cultured in high glucose.Diabetes Metab Res Rev,2004,20(4):330-336
[50]Jump DB.Dietary polyunsaturated fatty acids and regulation of gene transcription.Curt Opin Lipidol,2002,13(2):155-64
[51]Jump DB.The biochemistry of n-3 polyunsaturated fatty acids.J Biol Chem,2002,277(11):8755-8
[52]Sellmayer A,Hrboticky N,Weber PC.Lipids in vascular function.hipids,1999,34(suppl):S13-S18
[53]Aiello LP,Avery RL,Arrigg PG,et al.Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders.N Engl J Med,1994,331(22):1480-7.
[54]Miller JW,Adamis AP,Aiello LP.Vascular endothelial growth factor in ocular neovascularization and proliferative diabetic retinopathy.Diabetes Metab Rev,1997,13(1):37-50
[55]Sharp PS.The role of growth factors in the development of diabetic retinopathy.Metabolism,1995,44(10 Suppl 4):72-5
[56]Pfeiffer A,Middelberg-Bisping K,Drewes C,Schatz H..Elevated plasma levels of transforming growth factor-beta 1 in NIDDM. Diabetes Care, 1996, 19(10):1113-7
[57] Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet, 1994, 344(8934):1383-9
[58] Monique M, Pascal JV, et al. Glucose-mediated regulation of transforming growth factor-beta(TGF-β) and TGF-β receptor in human retinal endothial cells. Current Eye Res, 1999, 19(2):162-170
[59] Raul AP, Janice AJ, Bert MG. Effects of TGF-β andTGF-β neutralizing antibodies on the fibroblast-induced collagen gel contraction:implications for proliferative vitreoretinopathy.Invest Ophthalmol Vis Sci,1994, 35(7):2804-2809
[60] Massague J, Chen YG. Controlling TGF-beta signaling. Genes , 2000,14(6): 627-644
[61] Sanford LP, Ormsby I, Gittenberger-de Groot AC, et al. TGFbeta2 knockout mice have multiple developmental defects that are nonoverlapping with other TGFbeta knockout phenotypes. Development,1997,124(13):2659-70
[62] Antonelli-Orlidge A, Saunders KB, Smith SR, D'Amore PA. An activated form of transforming growth factor beta is produced by cocultures of endothelial cells and pericytes. Proc Natl Acad Sci U S A, 1989, 86 (12): 4544-8
[63] Wakefield LM, Smith DM, Flanders KC, Sporn MB. Latent transforming growth factor-beta from human platelets. A high molecular weight complex containing precursor sequences. J Biol Chem, 1988, 263(16):7646-54.
[64] Lyons RM , Keski-Oja J,ct al.Proteolytic activation of latent transforming growth factor beta in the control of epidermal proliferation. Cell Biol, 1998, 106:1659-1665
[65] Flaumenhaft R, Abe M, Mignatti P, et al. Basic fibroblast growth factor-induced activation of transforming growth factor beta in endothelial cell regulation of plasminogen activator activity.J Cell Biol, 1992,118(4):901-9
[66] Knott RM,Robertson M,et al.Glucose dependent regulation of D\A synthesis in bovine retinal endothelial cells.Curt Eye Res,1998,17:1-8
[67]Ishida K,Yamashita H,Katagiri H,Oka Y.Regulation of glucose transporter 1(GLUT1) gene expression by epidermal growth factor in bovine corneal endothelial cells.Jpn J Ophthalmol.1995,39(3):225-32
[68]Sohn M,Tan Y,Wang B,Klein RL,et al.Mechanisms of low-density lipoprotein-induced expression of connective tissue growth factor in human aortic endothelial cells.Am J Physiol Heart Circ Physiol,2006,290(4):H1624-34
[69]Saura M,Zaragoza C,Herranz B,et al.Nitric oxide regulates transforming growth factor-beta signaling in endothelial cells.Circ Res,2005,97(11):1115-23
[70]Hu T,Ramachandrarao SP,Siva S,et al.Reactive oxygen species production via NADPH oxidase mediates TGF-beta-induced cytoskeletal alterations in endothelial cells.Am Physiol Renal Physiol,2005,289(4):816-825
[71]Norata GD,Callegari E,MarchesiM,etal.High-density lipoproteins induce transforming growth factor-beta2 expression in endothelial cells.Circulation,2005,111(21):2805-2811
[72]Eisenstein R,GrantBD.Growth inhibitory activities in a vascular tissues arerecognized by antitransforming growth factor βantibodies.CurrEye Res,1991,10(2):157-162
[73]柳林,沈炜,刘志勇.转化生长因子β mRNA在糖尿病大鼠视网膜中的表达.中华眼科杂志,2003,39:46-47
[74]Wileman,Samantha M,Booth,et al.Regulation of plasminogen activation by TGF-β in cultured human retinal endothelial cells.British Ophthalmology,2000,84(4):417-422
[75]Grant MB,CaballeroS,Bush DM,Spoerri PE.Fibronectin fragments modulate human retinal capillary cell proliferation and migration.Diabetes,1998,47(8):1335-40
[76]Spirin KS,Saghizaden M,Lewin SL,etal.Basement membrane and growth factor gene expression in normal and diabetic human retinal.Curr Eye Res,1999,18(6):490-499.
[77]Hosoda Y,Okada M,Matsumura M,et al,Intravitreal neo-vascular tissue of proliferative diabetic retinopathy:an immunohistochemical study.Ophthalmic Res,1992,24(5):260-264
[78]Wiedemann P.Growth factors in retinal diseases:proliferative vitreoretinopathy,proliferative diabetic retinopathy,and retinal degeneration.Surv Ophthalmol,1992,36(5):373-84
[79]Pfeiffer A,Schatz H.Diabetic microvascular complications and growth factors.Exp Clin Endocri,1995,103(1):7-14
[80]Peer J,Fovverg R,Itin A,et al.Upregulated expression of vascular endothelial growth factor in proliferative diabetic retinopathy.Br Ophthalmol,1996,80(3):241-44
[81]Weller M,Fontana A.The failure of current immunotherapy for malignant giioma.Tumor-derived TGF-beta,T-cell apoptosis,and the immune privilege of the brain.Brain Res Brain Res Rev,1995,21(2):128-51.
[82]Derynck R,Zhang YE.Smad-dependent and Smad-independent pathways in TGF-beta family signalling.Nature,2003,425(6958):577-84
[83]Esser P,Bartz-Schmidt KU,Walter P,Kaszli F,Heimann K,Weller M.Apoptotic cell death in proliferative vitreoretinopathy.Ger J Ophthalmol,1996,5(2):73-8
[84]El Ghrably I,Powe DG,Orr G,Fischer D,et al.Apoptosis in proliferative vitreoretinopathy.Invest Ophthalmol Vis Sci.2004,45(5):1473-9
[85]Obata H,Kaburaki T,Kato M,Yamashita H.Expression TGF-beta type Ⅰ and typeⅡreceptors in rat eyes.Curr Eye Res,1996,15(3):335-340
[86]Zhu HJ,Burgess AW.Regulation of transforming growth factor beta signaling.Mol Cell Biol Res Commun,2001,4(6):321-330
[87]Chen RH,Ebner R,derynck R.inactivation of the type Ⅱ receptor cereals two receptor pathways for the diverse TGF-beta activities.Science,1993,260(5112):1335-8
[88] Sankar S, Mahooti-Brooks N, et al. Modulation of transforming growth factor beta receptor levels on microvascular endothelial cells during in vitro angiogenesis. Clin Invest, 1996, 97(6):1436-46
[89] Yingling JM, Wang XF, Bassing CH. Signaling by the transforming growth factor-beta receptors. Biochira Biophys Acta, 1995, 1242(2):115-36
[90] Segarini PR. TGF-beta receptors: a complicated system of multiple binding proteins. Biochim Biophys Acta, 1993, 1155(3):269-75
[91] Kenne WF, The role of lipids in renal disease:future challenges. Kidney Int , 2000:57(Suppl):S27-31
[92] Tedgui A, Mallat Z. Anti-inflammatory mechanisms in the vascular wall.Circ Res, 2001,88(9) :877-87
[93] Pintavorn P,Ballermann BJ. TGF-beta and the endothelium during immune injury. Kidney Int,1997,51(5):1401-12
[94] Pepper MS. Transforming growth factor-beta: vasculogenesis,angiogenesis, and vessel wall integrity. Cytokine Growth Factor Rev, 1997,8(1) :21-43
[95] Robertson AK, Rudling M, Zhou X, et al. Disruption of TGF-beta signaling in T cells accelerates atherosclerosis. J Clin Invest,2003, 112(9):1342-50
[96] Sanford LP, Ormsby I, Gittenberger-de Groot AC, et al. TGFbeta2 knockout mice have multiple developmental defects that are non-overlapping with other TGFbeta knockout phenotypes.Development, 1997,124(13):2659-70
[97] Oh SP, Seki T, Goss KA, Imamura T, Yi Y, Donahoe PK, Li L, Miyazono K, ten Dijke P, Kim S, Li E. Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis. Proc Natl Acad Sci U S A,2000 ,97(6): 2626-31
[98] Galvin KM, Donovan MJ, et al.A role for smad6 in development and homeostasis of the cardiovascular system.Nat Genet,2000, 24(2):171-179
[99] Sohn M, Tan Y, Klein RL, Jaffa AA. Evidence for low-density lipoprotein-induced expression of connective tissue growth factor in mesangial cells.Kidney Int,2005,67(4):1286-1296
[100]Chen YL,Wu HW,Jiang MJ,Transforming growth factor-betal gene and proteinexpression associated with atherogenesis of cholesterol-fed rabbits.Histol Histop-athol,2000,15(2):421-428
[101]Kanamasa K,Otani N,et al.Suppression of cell proliferation by tissue plasminogen activator during the early phase after balloon injury minimizes intimal hyperplasia in hypercholesterolemic rabbits.Cardiovasc Pharmacol,2001,37(2):155-62
[102]Ettore Porreca,Concetta Di Febbo,et al.Increased transforming growth factor-beta(1) circulating levels and production in human monocytes after3-hydroxy-3-methyl-glutaryl-coenzyme a reductase inhibition with pravastatin.Am Coll Cardiol,2002,39(11):1752-57
[103]Muhlfeld AS,Spencer MW,et al.Hyperlipidemia aggravates renal disease in B6.ROP Os/+ mice.Kidney Int,2004,66(4):1393-1402
[104]Kim SI,Han DC,Lee HB.Lovastatin inhibits transforming growth factor-betal expression in diabetic rat glomeruli and cultured rat mesangial cells,J Am Soc Nephrol,2000,11(1):80-7
[105]司晓芸,贾汝汉,黄从新,等.宽叶缬草对高胆固醇血症大鼠肾组织内TGFβ1表达的影响.中国中药杂志,2003,28(9):845-848
[1]Hueber A,Wiedemann P,Esser P,Heimann K.Basic fibroblast growth factor mRNA,bFGF peptide and FGF receptor in epiretinal membranes of intraocular proliferative disorders(PVR and PDR).Int Ophthalmol,1996-97,20(6):345-50
[2]Sivalingam A,Kenney J,Brown GC,Benson WE,Donoso L.Busic fibroblast growth factor levels in the vitreous of patients with proliferative diabetic retinopathy.Arch Ophthalmol,1990,108(6):869-72
[3]Hanneken A,de Juan E Jr,Lutty GA,et al.Altered distribution of basic fibroblast growth factor in diabetic retinopathy.Arch Ophthalmol,1991,109(7):1005-11
[4]Gaudric A,N'guyen T,Moenner M,et al.Quantification of angiogenesis due to basic fibroblast growth factor in a modified rabbit corneal model.Ophthalmic Res,1992,24(3):181-8
[5]董宇,隋东明,赵秀珍.吴家祥血管内皮生长因子及碱性成纤维细胞生长因子与糖尿病大鼠视网膜早期血管病变的关系。中华医学杂志,2003,83(11):996-99
[6]Papetti M,Shujath J,Riley KN,Herman IM.FGF-2 antagonizes the TGF-betal-mediated induction of pericyte alpha-smooth muscle actin expression:a role for myf-5 and Smad-mediated signaling pathways.Invest Ophthalmol Vis Sci,2003,44(11):4994-5005
[7]Christinger HW,Muller YA,BerLeau LT,et al.Crystallization of the receptor binding domain of vascular endothelial growth factor.Proteins,1996,26(3):353-7
[8]Aiello LP,Bursell SE,Clermont A,et al.Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta-isoform-selective inhibitor.Diabetes,1997,46(9):1473-80
[9]Amin RH,Frank RN,Kennedy A,Eliott D,Puklin JE,Abrams GW.Vascular endothelial growth factor is present in glial cells of the retina and optic nerve of human subjects with nonproliferative diabetic retinopathy,Invest Ophthalmol Vis Sci,1997,38(1):36-47
[10]Spirin KS,Saghizadeh M,Lewin SL,et al.Basement membrane and growth factor gene expression in normal and diabetic human retinas.Curr Eve Res,1999,18(6):190-9
[11]Adamis AP,Miller JW,Bernal MT,et al.Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy.Am J Ophthalmol,1994,118(4):445-50
[12]Malik RA,Li C,Aziz W,Olson JA,et al.Elevated plasma CD105 and vitreous VEGF levels in diabetic retinopathy.J Cell Mol Med,2005,9(3):692-7
[13]Qaum T,Xu Q,Joussen AM,et al.VEGF-initiated blood-retinal barrier breakdown in early diabetes.Invest Ophthalmol Vis Sci,2001,42(10):2408-13
[14]Perrin RM,Konopatskaya O,Qiu Y,Harper S,Bates DO,Churchill AJ.Diabetic retinopathy is associated with a switch in splicing from anti- to pro-angiogenic isoforms of vascular endothelial growth factor.Diabetologia,2005,48(11):2422-7
[15]Thieme H,Aiello LP,Takagi H,Ferrara N,King GL.Comparative analysis of vascular endothelial growth factor receptors on retinal and aortic vascular endothelial cells.Diabetes,1995,44(1):98-103
[16]Ambati J,Chalam KV,Chawla DK,et al.Elevated gamma-aminobutyric acid,glutamate,and vascular endothelial growth factor levels in the vitreous of patients with proliferative diabetic retinopathy.Arch Ophthalmol,1997,115(9):1161-6
[17]Ozaki H,Seo MS,Ozaki K,et al.Blockade of vascular endothelial cell growth factor receptor signaling is sufficient to completely prevent retinal neovascularization.Am J Pathol,2000,156(2):697-707
[18]Pfeiffer A,Middelberg-Bisping K,Drewes C,Schatz H..Elevated plasma levels of transforming growth factor-beta 1 in NIDDM.Diabetes Care,1996,19(10):1113-7
[19]Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease:the Scandinavian Simvastatin Survival Study(4S).Lancet,1994,344(8934):1383-9
[20]Monique M,Pascal JV,et al.Glucose-mediated regulation of transforming growth factor-beta(TGF-β) and TGF-β receptor in human retinal endothial cells. Current Eye Res, 1999, 19(2):162-170
[21] Raul AP,Janice AJ, Bert MG. Effects of TGF-pandTGF-β neutralizing antibodies on the fibroblast-induced collagen gel contraction:implications for proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci, 1994,35(7):2804-2809
[22] Eisenstein R, GrantBD. Growth inhibitory activities in a vascular tissues arerecognized by antitransforming growth factor β antibodies.CurrEye Res, 1991, 10(2):157-162
[23] Grant MB, Caballero S, Bush DM, Spoerri PE. Fibronectin fragments modulate human retinal capillary cell proliferation and migration.Diabetes,1998, 47(8):1335-40
[24] Spirin KS, Saghizaden M, Lewin SL, etal. Basement membrane and growth factorgene expression in normal and diabetic human retinal.Curr Eye Res, 1999, 18(6):490-499.
[25] Hosoda Y, Okada M, Matsumura M, et al, Intravitreal neo-vascular tissue of proliferative diabetic retinopathy:an immunohistochemical study. Ophthalmic Res, 1992, 24 (5):260-264
[26] Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature, 2003, 425(6958):577-84
[27] Esser P, Bartz-Schmidt KU, Walter P, Kaszli F, Heimann K, Weller M. Apoptotic cell death in proliferative vitreoretinopathy.Ger J Ophthalmol, 1996, 5(2):73-8
[28] El Ghrably I, Powe DG, Orr G, Fischer D, et al. Apoptosis in proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci.2004,45(5):1473-9
[29] Meyer-Schwickerath R, Pfeiffer A, et al. Vitreous levels of the insulin-like growth factors I and II, and the insulin-like growth factor binding proteins 2 and 3, increase in neovascular eye disease. Studies in nondiabetic and diabetic subjects. J Clin Invest., 1993, 92(6):2620-5
[30] Grant MB, Mames RN, Fitzgerald C, Ellis EA, Aboufriekha M, Guy J.Insulin-like growth factor I acts as an angiogenic agent in rabbit cornea and retina:comparative studies with basic fibroblast growth factor.Diabetologia,1993,36(4):282-91
[31]Layton CJ,Becket S,Osborne NN.The effect of insulin and glucose levels on retinal glial cell activation and pigment epithelium-derived fibroblast growth factor-2.Mol Vis,2006,12:43-54
[31]Danis RP,Bingaman DP.insulin-like growth factor-1 retinal microangiopathy in the pig eye.Ophthalmology,1997,104(10):1661-9
[32]Loukovaara S,Immonen IJ,Koistinen R,Rutanen EM,Hiilesmaa V,Loukovaara M,Kaaja RJ.The insulin-like growth factor system and Type 1 diabetic retinopathy during pregnancy.J Diabetes Complications,2005,19(5):297-304
[33]Spoerri PE,Afzal A,Li Calzi S,Shaw LC,Cai J,Pan H,Boulton M,Grant MB.Effects of VEGFR-1,VEGFR-2,and IGF-IR hammerhead ribozymes on glucose-mediated tight junction expression in cultured human retinal endothelial cells.Mol Vis,2006,12:32-42
[34]Averbukh E,Weiss O,Halpert M,Yanko R,Moshe R,Nephesh I,Flyvbjerg A,Yanko L,Raz I.Gene expression of insulin-like growth factor-Ⅰ,its receptor and binding proteins in retina under hypoxic conditions.Metabolism,1998,47(11):1331-6
[35]Sharp PS.The role of growth factors in the development of diabetic retinopathy.Metabolism,1995,44(10 Suppl 4):72-5
[36]Bergman PB,Moravski CJ,Edmondson SR,et al.Expression of the IGF system in normal and diabetic transgenic(mRen-2)27 rat eye.Invest Ophthalmol Vis Sci,2005,46(8):2708-15
[37]Ruberte J,Ayuso E,Navarro M,et al.Increased ocular levels of GF-1 in transgenic mice lead to diabetes-like eye disease.J Clin Invest,2004,113(8):1149-57
[38]Poulaki V,Joussen AM,Mitsiades N,et al.Insulin-like growth factor-Ⅰ plays a pathogenetic role in diabetic retinopathy.Am J Pathol,2004,165(2):457-69
[39]Pastor JC.Proliferative vitreoretinopathy:an overview.Surv Ophthalmol.1998,13(1):3-18
[40] Limb GA, Chignell AH, Green W, et al. Distribution of TNF alpha and its reactive vascular adhesion molecules in fibrovascular membranes of proliferative diabetic retinopathy. Br J Ophthalmol,1996,80(2): 168-73
[41] Demircan N, Safran BG, Soylu M, et al. Determination of vitreous interleukin-1 (IL—1) and tumour necrosis factor (TNF) levels in proliferative diabetic retinopathy. Eye. 2005,11
[42] Doganay S, Evereklioglu C, Er H, et al. Comparison of serum NO, TNF-alpha, IL-lbeta, sIL-2R, IL-6 and IL-8 levels with grades of retinopathy in patients with diabetes mellitus. Eye, 2002, 16(2):163-70
[43] Takashi Y, Tsugiyasu K,Yasutakak, etal. Inflammatory cytokines in vitreous fluid and serum of patients with diabetic vituro retinopathy. J Dibetes Compications, 2001, 15(5):257-259
[44] Hussain MJ, Peakman M,MallatiH. etal.Elevated serum levels of macrophage derived cytokines precede and accompany the onset on IDDM[J].Diabetologia 1999, 39(1):60-69
[45] Ben-Mahmud BM, Mann GE, Datti A, et al. Tumor necrosis factor-alpha in diabetic plasma increases the activity of core 2 GlcNAc-T and adherence of human leukocytes to retinal endothelial cells:significance of core 2 GlcNAc-T in diabetic retinopathy.Diabetes, 2004, 53(11):2968-76
[46] Joussen AM, Poulaki V, Mitsiades N, et al. Nonsteroidal anti-inflammatory drugs prevent early diabetic retinopathy via TNF-alpha suppression. FASEB J, 2002,16(3):438-40
[47] Funatsu H, YamashitaH, Sakata K, et al. Vitreous levels of vascular endothelial growth factor and intercellular adhesion molecule 1 are related to diabetic macular edema. Ophthalmology, 2005 ,112(5):806-16
[48] Limb GA, Chignell AH, Cole CJ, et al. Intercellular adhesion molecule-1 in proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci, 1997 ,38(5): 1043-8
[49] Chen W, Esselman WJ, Jump DB, Busik JV. Anti-inflammatory effect of docosahexaenoic acid on cytokine-induced adhesion molecule expression in human retinal vascular endothelial cells,lnvest Ophthalmol Vis Sci,2005,46(11):4342-7
[50]Yoshizawa M,Nagai Y,Ohsawa K,et al.Elevated serum levels of soluble vascular cell adhesion molecule-1 in NIDDM patients with proliferative diabetic retinopathy.Diabetes Res Clin Pract,1998,42(1):65-70
[51]Boulbou MS,Koukoulis GN,Petinaki EA,et al.Soluble adhesion molecules are not involved in the development of retinopathy in type 2 diabetic patients.Acta Diabetol,2004,41(3):118-22
[52]Chert W,Jump DB,Grant MB,Esselman WJ,Busik JV.Dyslipidemia,but not hyperglycemia,induces inflammatory adhesion molecules in human retinal vascular endothelial cells,Invest Ophthalmol Vis Sci,2003,;44(11):5016-22
[53]王国平,邓仲端,瞿智玲.氧化低密度和极低密度脂蛋白对单核细胞血小板衍生生长因子B链表达的影响[J].中国动脉硬化杂志,1995,3(3):221-223
[54]尹鸿操,刘佩毛.mm2LDL对内皮细胞转录因子NF2JB活性的影响[J].中国医学科学院学报,2001,23(4):312-316.
[55]Wiedemann P.Growth factors in retinal diseases:proliferative vitreoretinopathy,proliferative diabetic retinopathy,and retinal degeneration.Surv Ophthalmol,1992,36(5):373-84
[56]Cox OT,Simpson DA,Stitt AW,Gardiner TA.Sources of PDGF expression in murine retina and the effect of short-term diabetes.Mol Vis,2003,9:665-72
[57]Zhang SX,Wang JJ,Gao G,et al.Pigment epithelium-derived factor (PEDF) is an endogenous antiinflammatory factor.FASEB J,2006,20(2):323-5
[58]Yamagishi S,Inagaki Y,Nakamura K,Abe R,Shimizu T,Yoshimura A,Imaizumi T.Pigment epithelium-derived factor inhibits TNF-alpha-induced interleukin-6 expression in endothelial cells by suppressing NADPH oxidase-mediated reactive oxygen species generation.J Mol Cell Cardiol,2004,37(2):497-506
[59]Hammes HP,Lin J,Rennet O,Shani M,Lundqvist A,Betsholtz C,Brownlee M,Deutsch U.Pericytes and the pathogenesis of diabetic retinopathy.Diabetes,2002,51(10):3107-12
[60]刘丽娟,李茂欣,汤旭磊,高林,朱任之.糖尿病大鼠视网膜早期病变中PDGF-B的表达.第四军医大学学报,2005,26(23):2159-2161
[61]Munjal ID,McLean NV,Grant MB,Blake DA.Differences in the synthesis of secreted proteins in human retinal endothelial cells of diabetic and nondiabetic origin.Curr Eye Res,1994,13(4):303-10
[62]Patel B,Hiscott P,Charteris D,et al.Retinal and preretinal localisation of epidermal growth factor,transforming growth factor alpha,and their receptor in proliferative diabetic retinopathy.Br J Ophthalmol,1994,78(9):714-8
[63]Sato Y,Okamura K,Morimoto A,Hamanaka R,Hamaguchi K,Shimada T,Ono M,Kohno K,Sakata T,Kuwano M.Indispensable role of tissue-type plasminogen activator in growth factor-dependent tube formation of human microvascular endothelial cells in vitro.Exp Cell Res,1993,204(2):223-9