Umeda F, Yamauchi T, Inoguchi T, Nawata H
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Diabetes Res Clin Pract. 1992 May;16(2):109-15. doi: 10.1016/0168-8227(92)90081-2.
Human plasma-derived serum (PDS) stimulated the production of 6-keto-PGF1 alpha (a stable metabolite of PGI2) by cultured bovine aortic endothelial cells. The stimulation was both time- and dose-dependent. The main prostacyclin stimulatory activity (PSA) in human PDS remained biologically active after dialysis and was inhibited by the simultaneous addition of heparin. The maximum inhibition of PSA was obtained with 10 micrograms/ml heparin. PDS obtained from patients with non-insulin-dependent diabetes mellitus (NIDDM, n = 24) showed significantly less PSA than that from the control subjects (n = 11). A decrease in PSA was also found in diabetic patients using dialyzed PDS. The PSA in human PDS had a specific binding affinity to heparin-agarose and the bound PSA was eluted by a linear gradient of NaCl, which showed two major PSA peaks at 1.0 and 1.5 M NaCl. The dialyzed, mixed PDS from patients with NIDDM and the control subjects was independently applied to a heparin-agarose column and eluted by a linear gradient of NaCl. Comparing the PSA in each peak between the diabetic and the control dialyzed PDS, the PSA at 1.5 M NaCl was markedly decreased in the diabetic patients, but the PSA at 1.0 M NaCl did not change significantly. These observations suggest that the decreased PSA in human diabetic PDS may result mainly from the decrease in the activity of a specific non-dialyzed factor(s) which can bind to heparin. The decreased PSA in serum seems to be responsible in part for decreased PGI2 synthesis by the vascular wall of diabetics.
人血浆源性血清（PDS）可刺激培养的牛主动脉内皮细胞产生6-酮-前列腺素F1α（前列环素I2的稳定代谢产物）。这种刺激具有时间和剂量依赖性。人PDS中的主要前列环素刺激活性（PSA）在透析后仍保持生物活性，并被同时添加的肝素所抑制。用10微克/毫升肝素可获得对PSA的最大抑制作用。从非胰岛素依赖型糖尿病（NIDDM，n = 24）患者中获得的PDS显示出的PSA明显低于对照组（n = 11）。在使用透析后的PDS的糖尿病患者中也发现PSA降低。人PDS中的PSA与肝素琼脂糖具有特异性结合亲和力，结合的PSA通过NaCl线性梯度洗脱，在1.0和1.5 M NaCl处显示出两个主要的PSA峰。将来自NIDDM患者和对照组的透析混合PDS分别应用于肝素琼脂糖柱，并用NaCl线性梯度洗脱。比较糖尿病组和对照组透析后PDS各峰中的PSA，糖尿病患者中1.5 M NaCl处的PSA明显降低，但1.0 M NaCl处的PSA无明显变化。这些观察结果表明，人糖尿病PDS中PSA的降低可能主要是由于一种能与肝素结合的特定非透析因子活性降低所致。血清中PSA的降低似乎部分导致了糖尿病患者血管壁前列环素I2合成的减少。
