吡格列酮可预防健康受试者因缺血再灌注诱导的内皮功能障碍。

Pioglitazone prevents the endothelial dysfunction induced by ischemia and reperfusion in healthy subjects.

作者信息

Sakatani Yuka, Miyoshi Toru, Oe Hiroki, Noda Yoko, Ohno Yuko, Nakamura Kazufumi, Saito Yukihiro, Osawa Kazuhiro, Morita Hiroshi, Kohno Kunihisa, Ito Hiroshi

机构信息

Departments of *Cardiovascular Medicine; and †Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; and ‡Center of Ultrasonic Diagnostics, Okayama University Hospital, Okayama, Japan.

出版信息

J Cardiovasc Pharmacol. 2014 Oct;64(4):326-31. doi: 10.1097/FJC.0000000000000124.

DOI:10.1097/FJC.0000000000000124

PMID:24887686

Abstract

BACKGROUND

No study has investigated whether pioglitazone (an agonist of peroxisome proliferator-activated receptor gamma) protects against ischemia and reperfusion (IR)-induced endothelial dysfunction in humans.

METHODS AND RESULTS

In the first crossover study, 20 volunteers were randomized to 1 week of pioglitazone (30 mg/d, postoperatively) or control (no treatment). In the second single-arm study, 15 volunteers received pioglitazone and the cyclooxygenase-2 inhibitor meloxicam for 1 week. On day 7, endothelium-dependent flow-mediated dilation (FMD) of the distal brachial artery was measured before and after IR (15 minutes of ischemia followed by 15 minutes of reperfusion in the proximal upper arm). Pre-IR brachial-artery diameter and FMD were similar across the 2 sessions (control, pioglitazone) in protocol 1 and between the 2 protocols. IR significantly blunted FMD after no treatment (pre-IR FMD: 10.2% ± 2.6%; post-IR FMD: 3.5% ± 1.9%, P < 0.01) but not after pioglitazone administration (pre-IR FMD: 9.7% ± 2.5%; post-IR FMD: 8.8% ± 2.9%, P = 0.11). This protective effect was accompanied by an increase in serum levels of the antioxidant enzyme extracellular superoxide dismutase and was not affected by concomitant administration of the cyclooxygenase-2 inhibitor meloxicam (P = 0.10).

CONCLUSIONS

In humans, pioglitazone provides potent protection against IR-induced endothelial dysfunction.

摘要

背景

尚无研究探讨吡格列酮（过氧化物酶体增殖物激活受体γ激动剂）是否能预防人类缺血再灌注（IR）诱导的内皮功能障碍。

方法与结果

在第一项交叉研究中，20名志愿者被随机分为两组，一组接受吡格列酮治疗1周（术后30毫克/天），另一组为对照组（不治疗）。在第二项单臂研究中，15名志愿者接受吡格列酮和环氧化酶-2抑制剂美洛昔康治疗1周。在第7天，测量IR（上臂近端缺血15分钟后再灌注15分钟）前后肱动脉远端的内皮依赖性血流介导的血管舒张（FMD）。在方案1的两个疗程（对照组、吡格列酮组）以及两个方案之间，IR前肱动脉直径和FMD相似。未治疗时，IR显著减弱FMD（IR前FMD：10.2%±2.6%；IR后FMD：3.5%±1.9%，P<0.01），但吡格列酮给药后未出现这种情况（IR前FMD：9.7%±2.5%；IR后FMD：8.8%±2.9%，P = 0.11）。这种保护作用伴随着抗氧化酶细胞外超氧化物歧化酶血清水平的升高，并且不受环氧化酶-2抑制剂美洛昔康联合给药的影响（P = 0.10）。