Burn injury enhances brain prostaglandin E2 production through induction of cyclooxygenase-2 and microsomal prostaglandin E synthase in cerebral vascular endothelial cells in rats
Burn injury enhances brain prostaglandin E2 production through induction of cyclooxygenase-2 and microsomal prostaglandin E synthase in cerebral vascular endothelial cells in rats
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DOI：
10.1097/01.ccm.0000114576.60077.fc
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发表时间：
2004-03
影响因子：
8.8
通讯作者：
Yoko Ozaki-Okayama;K. Matsumura;T. Ibuki;M. Ueda;Y. Yamazaki;Yoshifumi Tanaka;Shigeo Kobayashi
中科院分区：
文献类型：
--
作者：
Yoko Ozaki-Okayama;K. Matsumura;T. Ibuki;M. Ueda;Y. Yamazaki;Yoshifumi Tanaka;Shigeo Kobayashi
目的 检测大鼠周围烧伤是否会升高中枢神经系统中的前列腺素 E2，并确定中枢神经系统中负责前列腺素 E2 合成的酶的表达位置。设计前瞻性对照动物研究。设置大学研究实验室。受试者斯普拉格-道利大鼠。干预措施 大鼠接受约 25% 全层烧伤或假治疗。损伤后36小时，采集脑脊液样本以测量前列腺素E2，并采集大脑和脊髓样本以进行免疫组织化学检测环氧合酶-2和微粒体型前列腺素E2合酶（负责前列腺素E2产生的酶）。测量和主要结果受伤大鼠脑脊液中前列腺素 E2 浓度显着升高，并且这种升高被环氧合酶 2 特异性抑制剂 NS398 抑制。仅在受伤大鼠中，在整个中枢神经系统的血管内皮细胞中检测到环氧合酶-2和微粒体型前列腺素E合酶蛋白，且没有区域差异。双重免疫荧光研究表明，环氧合酶-2 和微粒体型前列腺素 E 合酶在内皮细胞的核周区域共表达。结论这些结果表明外周烧伤诱导中枢神经系统内皮细胞中环氧合酶2和微粒体型前列腺素E合酶。这些酶可能会提高脑脊液中前列腺素 E2 的浓度，前列腺素 E2 是一种前列腺素，反过来又会激活中枢神经系统神经元上的前列腺素 E2 受体，参与烧伤后的一般症状。
ObjectivesTo examine whether peripheral burn injury in rats elevates prostaglandin E2 in the central nervous system and to determine where in the central nervous system enzymes responsible for prostaglandin E2 synthesis are expressed. DesignProspective controlled animal study. SettingUniversity research laboratory. SubjectsSprague-Dawley rats. InterventionsRats received either approximately 25% full-thickness burn injury or sham treatment. At 36 hrs after the injury, the cerebrospinal fluid was sampled to measure prostaglandin E2, and the brain and the spinal cord were sampled for immunohistochemical detection of cyclooxygenase-2 and microsomal-type prostaglandin E2 synthase, enzymes that are responsible for prostaglandin E2 production. Measurements and Main ResultsThe prostaglandin E2 concentration in the cerebrospinal fluid was significantly elevated in the injured rats, and this elevation was suppressed by a cyclooxygenase-2-specific inhibitor, NS398. Only in the injured rats, cyclooxygenase-2 and microsomal-type prostaglandin E synthase proteins were detected in vascular endothelial cells throughout the central nervous system with no regional difference. A double-immunofluorescence study revealed that cyclooxygenase-2 and microsomal-type prostaglandin E synthase were coexpressed in the perinuclear region of the endothelial cells. ConclusionsThese results indicate that peripheral burn injury induces cyclooxygenase-2 and microsomal-type prostaglandin E synthase in endothelial cells of the central nervous system. These enzymes likely elevate the cerebrospinal fluid concentration of prostaglandin E2, a prostanoid that, in turn, activates prostaglandin E2 receptors on the central nervous system neurons involved in the general symptoms following burn injury.