Lin Heng, Lin Teng-Nan, Cheung Wai-Mui, Nian Gau-Ming, Tseng Ping-Hui, Chen Shu-Fen, Chen Jean-Ju, Shyue Song-Kun, Liou Jun-Yang, Wu Cheng-Wen, Wu Kenneth K
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Circulation. 2002 Apr 23;105(16):1962-9. doi: 10.1161/01.cir.0000015365.49180.05.
We tested the hypothesis that bicistronic cyclooxygenase-1 (COX-1)/prostacyclin synthase (PGIS) and COX-1 gene transfer reduce cerebral infarct volume by augmenting synthesis of protective prostaglandins.
We infused into lateral ventricle of a rat stroke model recombinant adenoviruses (rAd) containing COX-1 (Adv-COX-1), COX-1 and PGIS (Adv-COX-1/PGIS), or Adv-PGK control vector, and we determined COX-1 and PGIS protein and eicosanoid levels and infarct volume. COX-1 and PGIS proteins were increased in a time-dependent manner. Adv-COX-1/PGIS infusion selectively augmented prostacyclin levels, with reduction of other eicosanoids in ischemic cortex and a significant reduction of infarct volume, even when the rAd was administered 5 hours after ischemia. Infusion of Adv-COX-1 also increased prostacyclin, suppressed leukotriene levels, and achieved a similar degree of cerebral protection. Its neuroprotection was abrogated by treatment with a selective COX-1 inhibitor.
COX-1/PGIS and COX-1 gene transfer reduce cerebral infarct volume by augmenting prostacyclin and suppressing leukotriene productions. COX-1-based gene transfer has potential for treating ischemic stroke.
我们验证了以下假说，即双顺反子环氧化酶-1（COX-1）/前列环素合酶（PGIS）及COX-1基因转移通过增加保护性前列腺素的合成来减少脑梗死体积。
我们将含有COX-1（Adv-COX-1）、COX-1和PGIS（Adv-COX-1/PGIS）或Adv-PGK对照载体的重组腺病毒（rAd）注入大鼠脑卒中模型的侧脑室，并测定COX-1和PGIS蛋白、类花生酸水平及梗死体积。COX-1和PGIS蛋白呈时间依赖性增加。Adv-COX-1/PGIS注入可选择性增加前列环素水平，并降低缺血皮层中其他类花生酸水平，且即使在缺血5小时后给予rAd，梗死体积也显著减小。Adv-COX-1注入也增加了前列环素，抑制了白三烯水平，并实现了类似程度的脑保护。其神经保护作用可被选择性COX-1抑制剂治疗所消除。
COX-1/PGIS和COX-1基因转移通过增加前列环素和抑制白三烯生成来减少脑梗死体积。基于COX-1的基因转移具有治疗缺血性脑卒中的潜力。
