Peroxisome proliferator-activated receptor-γ-agonist, rosiglitazone, promotes angiogenesis after focal cerebral ischemia
Peroxisome proliferator-activated receptor-γ-agonist, rosiglitazone, promotes angiogenesis after focal cerebral ischemia
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DOI：
10.1016/j.brainres.2006.03.114
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发表时间：
2006-06-06
期刊：
影响因子：
2.9
通讯作者：
Roh, Jae-Kyu
中科院分区：
文献类型：
--
作者：
Chu, Kon;Lee, Soon-Tae;Roh, Jae-Kyu
过氧化物酶体增殖物激活受体-γ (PPAR-γ) 激动剂罗格列酮不仅可以改善 II 型糖尿病患者的胰岛素抵抗，而且在神经或心血管疾病的各种动物模型中发挥广谱保护作用。我们研究了罗格列酮对局灶性脑缺血后血管生成和神经功能恢复的影响。在成年大鼠中诱导局灶性缺血前 7 天和诱导后 3 天（总共 10 天）给予罗格列酮（3 mg/kg 或 0.3 mg/kg，口服）。与具有剂量依赖性的缺血载体组相比，罗格列酮治疗组表现出神经系统改善增强、梗塞体积减少以及半球萎缩减少。与缺血载体组相比，罗格列酮治疗减少了 TUNEL+/激活的 caspase-3(+) 细胞、MPO+/Ox-42(+) 炎症细胞浸润、caspase-3 活性和 Bak(+) 细胞。与缺血载体组相比，罗格列酮组的血管表面积、血管分支点、血管长度和BrdU(+)内皮细胞数量均显着增加。罗格列酮增加缺血边缘周围的 eNOS 表达，同时下调 FasL。在这里，我们表明罗格列酮治疗可通过剂量依赖性诱导缺血耐受来增强血管生成和功能恢复。 (c) 2006 年，Elsevier B.V. 出版
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, rosiglitazone, not only improves insulin resistance in patients with type II diabetes but also exerts a broad spectrum protective effects in variable animal models of neurologic or cardiovascular diseases. We studied the effect of rosiglitazone on angiogenesis and neurological recovery after focal cerebral ischemia. Rosiglitazone (3 mg/kg or 0.3 mg/kg, p.o.) was administered for 7 days prior to and 3 days after the induction of focal ischemia (total 10 days) in adult rats. The rosiglitazone-treated group showed the enhanced neurologic improvement, the reduced infarction volume compared to the ischemia-vehicle group with dose dependency, and the reduced hemispheric atrophy. Rosiglitazone treatment reduced TUNEL+/activated caspase-3(+) cells, MPO+/Ox-42(+) inflammatory cell infiltrations, caspase-3 activity, and Bak(+) cells, as compared to the ischemia-vehicle group. The vascular surface area, the vascular branch points, the vascular length, and the number of BrdU(+) endothelial cells were significantly increased in the rosiglitazone group compared with the ischemia-vehicle group. Rosiglitazone increased eNOS expression around the ischemic margin with downregulation of FasL. Here, we show that rosiglitazone treatment enhances angiogenesis and functional recovery with dose-dependent induction of ischemic tolerance. (c) 2006 Published by Elsevier B.V.