Differential effects of peroxisome proliferator activator receptor-alpha and gamma ligands on intimal hyperplasia after balloon catheter-induced vascular injury in Zucker rats.
Differential effects of peroxisome proliferator activator receptor-alpha and gamma ligands on intimal hyperplasia after balloon catheter-induced vascular injury in Zucker rats.
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DOI：
10.1177/107424840300800407
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发表时间：
2003-12-01
影响因子：
2.6
通讯作者：
McNamara, Dennis B.
中科院分区：
文献类型：
--
作者：
Desouza, Cyrus V.;Murthy, S. N.;McNamara, Dennis B.
背景：2型糖尿病患者血管成形术后再狭窄率较高。过氧化物酶体增殖物激活物受体-α（PPAR）和γ配体，如非诺贝特和罗格列酮，分别显示对血管壁具有保护作用。我们研究了非诺贝特和罗格列酮对Zucker大鼠（胰岛素抵抗和2型糖尿病模型）球囊导管损伤后内膜增生的影响。方法和结果：三组13周龄雌性肥胖Zucker大鼠通过管饲法给予3 mg/kg/d罗格列酮（n=7）或150 mg/kg/d非诺贝特（n=6）的水性混悬液，或作为对照（n=9）。此外，对两组13周龄雌性瘦Zucker大鼠给予3 mg/kg/d罗格列酮（n=6）或作为对照（n=6）。给药1周后，建立颈动脉球囊损伤模型。给药持续3周。通过股动脉将2 mm球囊导管导入左颈动脉。将球囊充盈至4个大气压，持续20秒，然后回缩至2个大气压，并向下拖至主动脉。伤后3周处死大鼠。计算颈动脉内膜/中膜比值。罗格列酮治疗组（0.18 ± 0.29）与未治疗组（0.97 ± 0.13; P
Background: Patients with type 2 diabetes mellitus have a higher rate of restenosis following angioplasty. Peroxisome proliferator activator receptor-alpha (PPAR) and gamma ligands such as fenofibrate and rosiglitazone, respectively, have been shown to have protective effects on the vessel wall. We studied the effect of fenofibrate and rosiglitazone on intimal hyperplasia in the Zucker rat, a model for insulin resistance and type 2 diabetes mellitus, following balloon catheter-induced injury. Methods and Results: Three groups of 13-week-old female fatty Zucker rats were administered an aqueous suspension of either 3 mg/kg/d rosiglitazone (n=7) or 150 mg/kg/d fenofibrate (n=6) by gavage, or served as controls (n=9). In addition, two groups of 13-week-old female lean Zucker rats were either administered 3 mg/kg/d rosiglitazone (n=6) or served as controls (n=6). Carotid balloon injury was induced 1 week after the drugs were started. The drug administration was continued for 3 weeks. A 2-mm balloon catheter was introduced through the femoral artery to the left carotid. The balloon was inflated to 4 atmospheres for 20 seconds and then was deflated to 2 atmospheres and dragged down to the aorta. The rats were killed 3 weeks after the injury. The carotid intima/media ratio was calculated. Intimal hyperplasia after carotid balloon-induced injury in the fatty Zucker rats was significantly reduced in the group treated with rosiglitazone (0.18+-0.29) compared with the untreated group (0.97+-0.13; P