Lipsky P E
Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, 75235-8884, USA.
J Rheumatol Suppl. 1999 Apr;56:25-30.
The existence of two distinct isoforms of cyclooxygenase (COX), which convert arachidonic acid to prostanoids, is now well established. COX-1, which is constitutively expressed in many tissues (including the gastrointestinal tract, platelets, and kidney) is responsible for producing prostanoids that regulate normal housekeeping or physiologic functions. In contrast, COX-2 is the inducible form responsible for the production of prostanoids in response to a variety of evoking stimuli in different tissues and for mediation of inflammation and pain in certain diseases. Since the identification of COX-2, a great deal of research has been devoted to elucidating and understanding its molecular and physiologic characteristics. As a result of research into the differences between COX-1 and COX-2, new insights into the role of each isoform in normal homeostasis and in their responses to exogenous stimuli have emerged. Besides its induction in cells at inflammatory sites, COX-2 is known to be induced in the kidney in response to sodium depletion or in hyperfiltration states; in postsynaptic excitatory neurons in the brain after electroconvulsive stimulation, in the ovary and uterus during ovulation and implantation; in intestinal epithelium after bacterial infection; as well as in colon adenoma and carcinoma cells. These findings, largely from animal studies, have suggested a broader spectrum of biologic activity of COX-2 and potential alterations of specific physiologic or protective mechanisms by inhibition of COX-2, as well as potential new clinical targets of therapy with COX-2 inhibitors. As COX-2 appears to play an important role in pathologic processes other than pain and inflammation, ongoing research is investigating the potential utility of COX-2 inhibitors in other conditions, such as colonic polyposis, colorectal cancer, and Alzheimer's disease.
环氧化酶（COX）可将花生四烯酸转化为前列腺素，现已明确存在两种不同的同工型。COX-1在许多组织（包括胃肠道、血小板和肾脏）中组成性表达，负责产生调节正常内务或生理功能的前列腺素。相比之下，COX-2是诱导型同工型，负责在不同组织中响应各种诱发刺激产生前列腺素，并在某些疾病中介导炎症和疼痛。自COX-2被鉴定以来，大量研究致力于阐明和了解其分子和生理特征。对COX-1和COX-2差异的研究结果，使人们对每种同工型在正常体内平衡及其对外源刺激反应中的作用有了新的认识。除了在炎症部位的细胞中被诱导外，已知COX-2在肾脏中会因钠缺乏或高滤过状态而被诱导；在电惊厥刺激后大脑中的突触后兴奋性神经元中、排卵和着床期间的卵巢和子宫中；细菌感染后的肠上皮中；以及结肠腺瘤和癌细胞中被诱导。这些主要来自动物研究的发现表明，COX-2具有更广泛的生物活性，抑制COX-2可能会改变特定的生理或保护机制，同时也可能成为COX-2抑制剂治疗的新临床靶点。由于COX-2似乎在疼痛和炎症以外的病理过程中起重要作用，正在进行的研究正在调查COX-2抑制剂在其他病症中的潜在效用，如结肠息肉病、结直肠癌和阿尔茨海默病。
