Chowienczyk P J, Brett S E, Gopaul N K, Meeking D, Marchetti M, Russell-Jones D L, Anggård E E, Ritter J M
Department of Clinical Pharmacology, Centre for Cardiovascular Biology and Medicine, King's College, London, UK.
Diabetologia. 2000 Aug;43(8):974-7. doi: 10.1007/s001250051478.
AIMS/HYPOTHESIS: To determine whether raxofelast, a new water soluble antioxidant decreases oxidative stress and improves endothelial function in men with Type II (non-insulin dependent) diabetes mellitus.
We treated ten normotensive, normocholesterolaemic men with Type II diabetes and as controls ten healthy men matched with them for age with raxofelast (600 mg twice daily) for 1 week. Plasma 8-epi-PGF(2a), a non-enzymic oxidation product of arachidonic acid was measured by gas chromatography/mass spectrometry as an index of oxidative stress. Forearm vasodilator responses to brachial artery infusion of acetylcholine (7.5, 15 and 30 microg min(-1)) and of the nitric oxide donor nitroprusside (1, 3 and 10 microg min(-1)) were measured by strain gauge plethysmography.
Plasma concentrations of 8-epi-PGF(2a), were greater in diabetic than in control men (0.99 +/- 0.20 vs 0.18 +/- 0.01 nmol 1(-1), means +/- SEM, p < 0.001) and fell after raxofelast (from 0.99 +/- 0.20 to 0.47 +/- 0.07 nmol 1(-1), p < 0.05) in diabetic men but not in control men. Blood flow responses to acetylcholine were lower (p < 0.05) in diabetic than in control men (7.4 +/- 1.0 vs 12.9 +/- 2.3 ml min(-1) x 100 ml(-1) for the highest dose). In diabetic men, but not in control men, raxofelast increased (p < 0.05) blood flow responses to acetylcholine (from 7.4 +/- 1.0 m x min(-1) x 100 ml(-1) to 11.3 +/- 2.3 ml x min(-1) x 100 ml(-1) at highest dose). Blood flow responses to nitroprusside were similar in control and diabetic men and in both groups were similar before and after raxofelast.
CONCLUSION/INTERPRETATION: Oral treatment with raxofelast for 1 week reduces oxidative stress and improves endothelial function in men with Type II diabetes.
目的/假设：确定新型水溶性抗氧化剂雷索非拉斯特是否能降低2型（非胰岛素依赖型）糖尿病男性患者的氧化应激并改善其内皮功能。
我们对10名血压正常、胆固醇正常的2型糖尿病男性患者进行治疗，并以10名年龄匹配的健康男性作为对照，给予雷索非拉斯特（每日两次，每次600毫克），持续1周。通过气相色谱/质谱法测定血浆8-表-前列腺素F2α（8-epi-PGF2α），这是一种花生四烯酸的非酶氧化产物，作为氧化应激指标。采用应变片体积描记法测量前臂对肱动脉输注乙酰胆碱（7.5、15和30微克/分钟）和一氧化氮供体硝普钠（1、3和10微克/分钟）的血管舒张反应。
糖尿病男性患者血浆8-epi-PGF2α浓度高于对照组男性（0.99±0.20对0.18±0.01纳摩尔/升，均值±标准误，p<0.001），雷索非拉斯特治疗后糖尿病男性患者血浆8-epi-PGF2α浓度下降（从0.99±0.20降至0.47±0.07纳摩尔/升，p<0.05），而对照组男性患者未下降。糖尿病男性患者对乙酰胆碱的血流反应低于对照组男性（最高剂量时分别为7.4±1.0对12.9±2.3毫升/分钟×100毫升-1，p<0.05）。雷索非拉斯特使糖尿病男性患者对乙酰胆碱的血流反应增加（p<0.05）（最高剂量时从7.4±1.0毫升/分钟×百毫升-1增至11.3±2.3毫升/分钟×百毫升-1），而对照组男性患者未出现这种情况。对照组和糖尿病男性患者对硝普钠的血流反应相似，且在雷索非拉斯特治疗前后两组反应均相似。
结论/解读：雷索非拉斯特口服治疗1周可降低2型糖尿病男性患者的氧化应激并改善其内皮功能。
