Umeda F, Kunisaki M, Inoguchi T, Nawata H
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Diabetes Res Clin Pract. 1990 Jan;8(2):137-44. doi: 10.1016/0168-8227(90)90024-n.
Reduced prostacyclin (PGI2) production by the vascular wall has been proposed as one of the possible causes of diabetic vascular complications. We found an activity which stimulated PGI2 production by cultured endothelial cells (PGI2-stimulatory activity, PSA) in human plasma-derived serum (PDS). The PSA was less in patients with diabetes mellitus. The present study was undertaken to evaluate how metabolic factors relevant to diabetic angiopathy modify the PSA. Pooled PDS was prepared from 10 healthy volunteers. The 6-keto-PGF1 alpha (6KF, a stable metabolite of PGI2) production by cultured bovine aortic endothelial cells was maximally stimulated by Dulbecco's modified Eagle's medium (DMEM) containing 10% pooled PDS after incubation for 60 min. The production of 6KF was reduced in a dose-dependent manner by the addition of 10% pooled PDS with glucose and linoleic acid hydroperoxide (lipid peroxide). In contrast, human low density lipoprotein (LDL) and linoleic acid (unsaturated fatty acid) enhanced the production of 6KF by 10% pooled PDS in a dose-dependent manner. Insulin, however, showed no effect on the production of 6KF by 10% pooled PDS. These results suggest that the reduced PSA in diabetics may be the result, in part, of a modification of the PSA by diabetic metabolic factors such as glucose and lipid peroxide.
血管壁前列环素（PGI2）生成减少被认为是糖尿病血管并发症的可能原因之一。我们在人血浆来源血清（PDS）中发现了一种能刺激培养的内皮细胞生成PGI2的活性物质（PGI2刺激活性，PSA）。糖尿病患者的PSA较低。本研究旨在评估与糖尿病血管病变相关的代谢因素如何改变PSA。从10名健康志愿者中制备混合PDS。培养的牛主动脉内皮细胞在含有10%混合PDS的杜尔贝科改良伊格尔培养基（DMEM）中孵育60分钟后，6-酮-PGF1α（6KF，PGI2的稳定代谢产物）的生成受到最大刺激。加入含有葡萄糖和氢过氧化亚油酸（脂质过氧化物）的10%混合PDS后，6KF的生成呈剂量依赖性降低。相反，人低密度脂蛋白（LDL）和亚油酸（不饱和脂肪酸）以剂量依赖性方式增强了10%混合PDS对6KF的生成。然而，胰岛素对10%混合PDS生成6KF没有影响。这些结果表明，糖尿病患者PSA降低可能部分是由于糖尿病代谢因素如葡萄糖和脂质过氧化物对PSA的改变所致。
