Bakillah A, Grigorova-Borsos A M, Guillot R, Urios P, Sternberg M
Equipe de Recherches sur la Biochimie et la Pharmacologie des Vaisseaux et du Rein, Faculté de Médecine Broussais-Hôtel-Dieu, U.F.R. Biomédicale des Saints-Pères, Université de Paris V & VI, Paris.
Diabetologia. 1996 Jun;39(6):641-8. doi: 10.1007/BF00418535.
Diabetic microangiopathy is characterized by a thickening of capillary basement membranes associated with type IV collagen accumulation. An increase in type IV collagen content of the aortic wall is also observed in macroangiopathy. In order to analyse the importance of the polyol pathway in the development of the collagen metabolism alterations seen in diabetic angiopathy and their prevention by aldose reductase inhibitors, we have studied the effects of sorbinil on the high glucose-induced stimulation of type IV collagen biosynthesis in human umbilical vein endothelial cells. Primary cultures were exposed to high glucose (16.7 mmol/l), with and without 0.11 mmol/l sorbinil, for 3 or 6 days after beginning of confluence. We measured the soluble type IV collagen secreted into the culture medium and the insoluble type IV collagen accumulated in the extracellular matrix and cells, by ELISA. We also studied [14C]proline incorporation into the newly synthesized collagenous and total proteins in the culture supernatant and in the extracellular matrix and cell fraction. High glucose decreased the number of cells and increased the amount of type IV collagen in the culture supernatant and in the extracellular matrix and cell fraction. It also increased proline incorporation into the newly synthesized collagenous and total proteins in the culture supernatant and in the extracellular matrix and cell fraction. Sorbinil corrected all these high glucose-induced alterations. The corrective effects of sorbinil on the proliferation and on type IV collagen metabolism of endothelial cells cultured in high glucose may be attributed to prevention of polyol pathway dysregulation.
糖尿病微血管病变的特征是毛细血管基底膜增厚并伴有IV型胶原积聚。在大血管病变中也观察到主动脉壁IV型胶原含量增加。为了分析多元醇途径在糖尿病性血管病变中所见胶原代谢改变的发生及其被醛糖还原酶抑制剂预防中的重要性，我们研究了索比尼尔对高糖诱导的人脐静脉内皮细胞IV型胶原生物合成刺激的影响。原代培养物在汇合开始后，分别在有和没有0.11 mmol/l索比尼尔的情况下，暴露于高糖（16.7 mmol/l）中3天或6天。我们通过ELISA法测量了分泌到培养基中的可溶性IV型胶原以及在细胞外基质和细胞中积累的不溶性IV型胶原。我们还研究了[14C]脯氨酸掺入培养上清液、细胞外基质和细胞部分中新合成的胶原和总蛋白中的情况。高糖减少了细胞数量，并增加了培养上清液、细胞外基质和细胞部分中IV型胶原的量。它还增加了脯氨酸掺入培养上清液、细胞外基质和细胞部分中新合成的胶原和总蛋白中的量。索比尼尔纠正了所有这些高糖诱导的改变。索比尼尔对在高糖中培养的内皮细胞增殖和IV型胶原代谢的纠正作用可能归因于对多元醇途径失调的预防。
