Cyclooxygenase-2, prostaglandin synthases, and prostaglandin H2 metabolism in traumatic brain injury in the rat
Cyclooxygenase-2, prostaglandin synthases, and prostaglandin H2 metabolism in traumatic brain injury in the rat
复制标题
DOI：
10.1089/089771502760341965
复制
发表时间：
2002-09-01
影响因子：
4.2
通讯作者：
Oliw, EH
中科院分区：
文献类型：
--
作者：
Kunz, T;Marklund, N;Oliw, EH
炎症介质在创伤性脑损伤（TBI）中起重要作用。本研究的目的是研究环氧化酶-2 （COX-2）、前列腺素E （PGE）和PGD合成酶的表达以及PGH(2)在两种创伤性脑损伤大鼠模型中的代谢。液体冲击损伤（FPI）可诱导双侧齿状回和皮层COX-2 mRNA表达，而控制性皮质挫伤损伤（CCC）可诱导同侧齿状回COX-2 mRNA表达，并通过原位杂交检测其在皮质中表达强烈。诱导作用在24小时内消退。在这些区域检测到COX-2免疫反应性，并在CCC后至少72小时内持续在同侧皮质。COX-2诱导区与TUNEL染色共定位，提示COX-2表达与细胞损伤之间存在联系。COX-2形成PGH(2)，可通过酶促和非酶促机制异构化为PGD(2)、PGE(2)和PGF（2alpha）。原位杂交显示脉络膜丛中存在PGD合成酶和微粒体PGE合成酶mRNA。微体PGE合成酶在FPI后呈双侧诱导，在CCC后呈单侧诱导。液相色谱-质谱联用分析表明，正常和损伤后的皮质和海马低速上清以PGH(2)转化为PGD(2)为主要产物。PGD(2)在脑匀浆中脱水成生物活性化合物，例如15-脱氧- δ (12,14)-PGJ(2)。因此，在没有PGD和微粒体PGE合成酶神经元诱导的情况下，脑外伤后某些神经元中COX-2增加，表明PGH(2)可能通过非酶机制分解为PGD(2)及其脱水产物，或通过低组成水平的PGD合成酶分解为PGD(2)。
Inflammatory mediators are important in traumatic brain injury (TBI). The objective of the present study was to investigate the expression of cyclooxygenase-2 (COX-2), prostaglandin E (PGE) and PGD synthases, and PGH(2) metabolism in two rat models of TBI. Fluid percussion injury (FPI) resulted in bilateral induction of COX-2 mRNA in the dentate gyri and the cortex, whereas controlled cortical contusion injury (CCC) induced COX-2 mRNA in the ipsilateral dentate gyrus and intensely in the cortex as judged by in situ hybridization. The induction subsided within 24 h. COX-2 immunoreactivity was detectable in these areas and persisted in the ipsilateral cortex for at least 72 h after CCC. Regions with COX-2 induction co-localized with TUNEL staining, suggesting a link between COX-2 expression and cell damage. COX-2 forms PGH(2), which can be isomerized to PGD(2), PGE(2), and PGF(2alpha) by enzymatic and non-enzymatic mechanisms. In situ hybridization showed that mRNA of PGD synthase and microsomal PGE synthase were present in the choroid plexus. The microsomal PGE synthase was induced bilaterally after FPI and unilaterally after CCC. Liquid chromatography-mass spectrometry showed that low speed supernatant of normal and traumatized cortex and hippocampus transformed PGH(2) to PGD(2) as main product. PGD(2) was dehydrated in brain homogenates to biological active compounds, for example, 15-deoxy-Delta(12,14)-PGJ(2). Thus COX-2 increases in certain neurons following TBI without neuronal induction of PGD and microsomal PGE synthases, suggesting that PGH(2) may decompose to PGD(2) and its dehydration products by nonenzymatic mechanisms or to PGD(2) by low constitutive levels of PGD synthase.