Catella F, Nowak J, Fitzgerald G A
Am J Med. 1986 Aug 25;81(2B):23-9. doi: 10.1016/0002-9343(86)90905-8.
Enzymatic metabolites of arachidonic acid (eicosanoids) have potent biologic actions in vitro that suggest their pathophysiologic importance in vivo. To address this possibility, analytic methodology has been developed to permit study of the formation of these compounds in vivo. Both radioimmunoassay and gas chromatography-mass spectrometry have been used to measure stable but biologically inactive metabolites of the eicosanoids. Although indirect, such measures are presently the most reliable, because superfusion-bioassay lacks the specificity and precision necessary for quantitative analysis of eicosanoid formation in vivo. Measurement of eicosanoids and their hydration products and metabolites in urine represents a non-invasive approach to the assessment of eicosanoid biosynthesis. Although a tissue of origin cannot be ascribed definitely to a compound measured in urine, corroborative evidence can be obtained to indicate the predominant tissue source under physiologic and pathologic conditions. This relates particularly to the distinction between renal and extrarenal biosynthesis of these compounds. Although similar limitations apply to the measurement of eicosanoids in plasma, these may also be confounded by sources of artifact related to blood withdrawal. In the case of thromboxane B2, these concerns have been addressed by the development of methods to measure its enzymatic metabolites in plasma. Finally, formation of eicosanoids may be studied in localized compartments such as lavage or synovial fluid. Such an approach has recently provided biochemical evidence for increased formation of prostacyclin and prostaglandin E2 at the platelet-vascular interface during selective inhibition of thromboxane synthase in humans.
花生四烯酸的酶促代谢产物（类二十烷酸）在体外具有强大的生物学作用，这表明它们在体内具有病理生理学重要性。为了探究这种可能性，已开发出分析方法来研究这些化合物在体内的形成过程。放射免疫测定法和气相色谱 - 质谱联用技术都已被用于测量类二十烷酸的稳定但无生物活性的代谢产物。尽管这些方法是间接的，但目前是最可靠的，因为灌流生物测定法缺乏对体内类二十烷酸形成进行定量分析所需的特异性和精确性。测量尿液中的类二十烷酸及其水合产物和代谢产物是评估类二十烷酸生物合成的一种非侵入性方法。虽然无法明确将尿液中检测到的化合物归属于特定的组织来源，但可以获得佐证证据以表明在生理和病理条件下主要的组织来源。这对于区分这些化合物的肾脏和肾外生物合成尤为重要。尽管在血浆中测量类二十烷酸也存在类似的局限性，但这些局限性可能还会因与采血相关的假象来源而变得更加复杂。对于血栓素B2，通过开发在血浆中测量其酶促代谢产物的方法解决了这些问题。最后，可以在局部腔室如灌洗液或滑液中研究类二十烷酸的形成。最近，这种方法为在人类血栓素合酶受到选择性抑制期间血小板 - 血管界面处前列环素和前列腺素E2形成增加提供了生化证据。
