The roles of the COXs in normal physiology and in pathological conditions

这些研究的主要目的是阐明COX-1和COX-2在正常生理和不同病理状态下的个体作用。具体地说，实验室内的工作主要集中在使用COX-2缺陷的小鼠ES细胞和COX特异性抑制剂来研究COX-2在内皮细胞发育和动脉瘤形成中的作用。免疫组织化学方法检测血管内皮细胞分化程度，免疫组织化学方法检测CD-31染色的细胞索状结构，Western分析血管内皮生长因子受体和环氧合酶-2的表达。我们的研究表明，COX-2的缺失在体外抑制了小鼠ES细胞向内皮样细胞的分化。然而，对COX-2选择性抑制剂的研究表明，即使在COX-2-/-ES细胞中，COX-2抑制剂也能阻止内皮样细胞的发育，这表明COX-2非依赖机制起作用。 此外，正在开发研究COX-2在动脉瘤形成中的作用的小鼠模型，初步研究表明，COX-2缺乏可以减轻小鼠心脏和腹部血管系统的炎症反应。此外，合作研究还表明，COX-2缺乏会增加小鼠大脑中的炎症反应。

The major goals of these studies are to elucidate the individual roles of COX-1 and COX-2 in normal physiology and in various pathological states. Specifically, effort within the laboratory has focused on using COX-2 deficient mouse ES cells and COX specific inhibitors to study the roles of COX-2 in endothelial cell development and aneurysm formation. Endothelial cell ifferentiation was measured immunohistochemically by the appearance of CD-31 staining cord like structures of cells and the appearance of VEGF receptors and COX-2 on Western analysis. Our studies indicated that the deficiency of COX-2 inhibited mouse ES cell differentiation into endothelial-like cells in vitro. However, studies with COX-2 selective inhibitors have indicated that the COX-2 inhibitors blocked endothelial-like cell development even in COX-2-/- ES cells, suggesting that a COX-2 independent mechanism was responsible. In addition, a mouse model to study the contributions of COX-2 to aneurysm formation is being developed and initial studies indicate that COX-2 deficiency attenuates inflammatory responses in the mouse heart and abdominal vasculature. Also, collaborative studies have demonstrated that COX-2 deficiency increased inflammatory responses in the mouse brain.