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糖尿病视网膜病变中红细胞膜蛋白的结构改变。

Structural alterations of the erythrocyte membrane proteins in diabetic retinopathy.

作者信息

Petropoulos Ioannis K, Margetis Panagiotis I, Antonelou Marianna H, Koliopoulos John X, Gartaganis Sotirios P, Margaritis Lukas H, Papassideri Issidora S

机构信息

Department of Ophthalmology, University Hospitals of Geneva, 22 Alcide-Jentzer Street, 1211 Geneva 14, Switzerland.

出版信息

Graefes Arch Clin Exp Ophthalmol. 2007 Aug;245(8):1179-88. doi: 10.1007/s00417-006-0500-6.

Abstract

BACKGROUND

Several rheological disorders of the erythrocytes, such as increased aggregation and decreased deformability, have been observed in diabetes mellitus and have been implicated in the development of diabetic microangiopathy. Structural alterations of the erythrocyte membrane proteins caused by the diabetic process may be at the origin of those observations. In the present study, we searched for erythrocyte membrane protein alterations in diabetic retinopathy.

METHODS

We examined peripheral blood samples from 40 type-2 diabetic patients with diabetic retinopathy of variable severity (19 males and 21 females, mean age 66.8 years, Group A) and we compared them with samples from 19 type-2 diabetic patients without diabetic retinopathy (13 males and six females, mean age 66.5 years, Group B) and 16 healthy volunteers (eight males and eight females, mean age 65.6 years, Group C). Erythrocyte membrane ghosts from all samples were subjected to SDS-PAGE, and the electrophoretic pattern of transmembrane and cytoskeletal proteins was analysed for each sample. The protein quantification of each electrophoretic band was accomplished through scanning densitometry.

RESULTS

No significant deviations from normal electrophoresis were observed in Groups B and C, apart from an increase in band 8 in two samples from Group B (11%). In contrast, in 14 samples from Group A (35%) we detected increases in protein band 8 and/or membrane-bound haemoglobin along with a decrease in spectrin. Moreover, increased mobility of band 3, an aberrant high molecular weight (MW) (> 255 kDa) band and a low MW (42 kDa) band were evident in ten samples from Group A (25%). Glycophorins were altered in 46% of Group-A patients versus 38% of Group-B patients. Females and patients with long duration of diabetes presented more electrophoretic abnormalities.

CONCLUSIONS

Structural alterations of the erythrocyte membrane proteins are shown for the first time in association with diabetic retinopathy. Their detection may serve as a blood marker for the development of diabetic microangiopathy. Further studies are needed to assess whether pharmaceutical intervention to the rheology of erythrocytes can prevent or alleviate microvascular diabetic complications.

摘要

背景

在糖尿病患者中已观察到几种红细胞流变学紊乱,如聚集增加和变形性降低,这些与糖尿病微血管病变的发展有关。糖尿病进程导致的红细胞膜蛋白结构改变可能是这些观察结果的根源。在本研究中,我们探寻糖尿病视网膜病变中红细胞膜蛋白的改变。

方法

我们检测了40例患有不同严重程度糖尿病视网膜病变的2型糖尿病患者(19例男性和21例女性,平均年龄66.8岁,A组)的外周血样本,并将其与19例无糖尿病视网膜病变的2型糖尿病患者(13例男性和6例女性,平均年龄66.5岁,B组)以及16名健康志愿者(8例男性和8例女性,平均年龄65.6岁,C组)的样本进行比较。对所有样本的红细胞膜影进行十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE),并分析每个样本跨膜蛋白和细胞骨架蛋白的电泳图谱。通过扫描密度测定法完成每个电泳条带的蛋白质定量。

结果

除了B组的两个样本(11%)中条带8增加外,B组和C组未观察到与正常电泳有显著偏差。相比之下,在A组的14个样本(35%)中,我们检测到条带8和/或膜结合血红蛋白增加,同时血影蛋白减少。此外,在A组的10个样本(25%)中,条带3迁移率增加、出现异常的高分子量(MW)(>255 kDa)条带和低分子量(42 kDa)条带明显可见。A组46%的患者糖蛋白发生改变,而B组为38%。女性和糖尿病病程长的患者出现更多的电泳异常。

结论

首次显示红细胞膜蛋白的结构改变与糖尿病视网膜病变有关。它们的检测可作为糖尿病微血管病变发展的血液标志物。需要进一步研究来评估对红细胞流变学的药物干预是否可以预防或减轻糖尿病微血管并发症。

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