中国作者重要发表 - 培哚普利对糖尿病性视网膜病变的保护性作用与血管内皮生长因子对色素上皮衍生因子比例的降低相关：涉及一种线粒体活性氧途径



培哚普利对糖尿病性视网膜病变的保护性作用与血管内皮生长因子对色素上皮衍生因子比例的降低相关：涉及一种线粒体活性氧途径





Protective effect of perindopril on diabetic retinopathy is associated with decreased vascular endothelial growth factor-to-pigment epithelium-derived factor ratio: Involvement of a mitochondria-reactive oxygen species pathway





Zheng Z., Chen H., Ke G., Fan Y., Zou H., Sun X., Gu Q., Xu N., Ho P.C.P. 2009/5/29 18:38:57

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Diabetes, 2009, Volume 58, Issue 4




OBJECTIVE-This study aimed to verify whether the decreased vascular endothelial growth factor (VEGF)-to-pig- ment epithelium-derived factor (PEDF) ratio can serve as an indicator for the protective effect of angiotensin-converting enzyme inhibitors (ACEIs) on diabetic retinopathy (DR) and to investigate the role of mitochondrial reactive oxygen species (ROS) in the downregulated VEGF-to-PEDF ratio. RESEARCH DESIGN AND METHODS-Diabetic rats and control animals were randomly assigned to receive perindopril or vehicle for 24 weeks, and bovine retinal capillary endothelial cells (BRECs) were incubated with normal or high glucose with or without perindopril. VEGF, PEDF, PPARγ, and uncoupling protein-2 (UCP-2) in the rat retinas or BREC extracts were examined by Western blotting and real-time RT-PCR. The levels of VEGF and PEDF in cell culture media were examined by ELISA. Mitochondrial membrane potential (Δψm) and ROS production were assayed using JC-1 or CM-H2DCFDA. RESULTS-The VEGF-to-PEDF ratio was increased in the retina of diabetic rats; perindopril lowered the increased VEGF-to- PEDF ratio in diabetic rats and ameliorated the retinal damage. In BRECs, perindopril lowered the hyperglycemia-induced elevation of VEGF-to-PEDF ratio by reducing mitochondrial ROS. We found the decreased ROS production was a result of perindopril- induced upregulation of PPARγ and UCP-2 expression and the subsequent decrease of Δψm. CONCLUSIONS-It is concluded that the protective effect of ACEI on DR is associated with a decreased VEGF-to-PEDF ratio, which involves the mitochondria-ROS pathway through PPARγ-mediated changes of UCP-2. This study paves a way for future application of ACEI in treatment of DR. © 2009 by the American Diabetes Association.



Correspondence Address: Xu, N.; Department of Ophthalmology, First People's Hospital of Shanghai, Shanghai Jiaotong University, Shanghai, China; email: xuxun60@yahoo.com.cn



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疾病资源中心

高血压	慢性阻塞性肺病
脂肪性肝病	糖尿病
卒中	肺癌
冠心病	子宫内膜异位症
结直肠癌	乳腺癌
心力衰竭	心律失常

病例分析

甲状腺功能亢进合并黄疸

王燕燕王曙

上海交通大学附属瑞金医院内分泌科

患者，女，69岁。2009年1月无明显诱因下出现乏力，当时程度较轻，未予以重视。2009年3月患者乏力症状加重，尿色逐渐加深，大便习惯改变，颜色变淡。4月18日入我院感染科治疗，诉轻度头晕、心慌，体重减轻10kg。无肝区疼痛，无发热，无腹痛、腹泻、腹胀、里急后重，无恶性、呕吐等。入院半月前于外院就诊，查肝功能：ALT 601IU/L，AST 785IU/L，TBIL 97.7umol/L，白蛋白 41g/L，甲状腺功能：游离T3 30.6pmol/L，游离T4 51.9pmol/L，心电图示快速房颤。

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