选择性COX2抑制剂的研究进展.docVIP

选择性COX-2抑制剂的研究进展 李国俊 (安徽中医药大学，12药S (3)班 环氧化酶(Cyclooxygenase, COX)是花生四埔酸(AA)转化成前列腺素 (PGs)过程中重要的限速酶。它催化产生的PGs参与机体多种生理及病理生 理过程，如炎症、发热、出凝血过程等。1991年证实环氧化酶(COX)有两个 亚型：COX-1和C0X-2,环氧化酶(cox)有两种同工酶参与PG的合成。诱导酶 COX-2参与关节炎的疼痛和炎症有关，而组成酶COX-1与胃和十二指肠部位 的胃保护性PG的合成有关。传统NSAIDs如阿斯匹林、吲哚美辛、双氯芬酸、 萘普生、等对COXI和C0x2无选择性，可称之为非选择性COX抑制剂 (Nomelective COX inhibitor)。其对COX2的抑制作用是其治疗基础，而对 COX-1的抑制作用则成为严重的全消化道损伤的原因。一些现有的NSAIDS, 低剂量时对C0X2优先抑制，称为倾向性C0X-2抑制剂(referential COX-2 inhibitor),如美洛昔康(me丨ox i cam)、尼美舒利(n i mesu I i de)、依托度酸 (etodolac)。此类药物的临床疗效与非选择性COX抑制剂相当，但胃肠道不 良反应发生率较低。特异性C0X-2抑制剂(specific COX-2 inhibitor), 如塞莱昔布(ce I ecox i b)、罗非昔布(r of ecox i b)、伐地昔布(va I decox i b)、 帕瑞昔布和艾托昔布，在治疗范围内很少或没有COX-1作用。临床研究表明： 特异性COX-2抑制剂的胃肠道安全性优于传统的NSAIDs，但若干研究表明长 期应用特异性C0X-2抑制剂可能增加心血管事件的风险，如心肌梗塞、脑 卒中。塞莱昔布、罗非昔布和伐地昔布暴露出的问题说明虽然特异性C0X-2 抑制剂在胃肠道安全性方面有显著的优势，但长期用药的安全性仍需开展 进一步的研究和评价。 关键词环氧化酶、COX-1、C0X-2、花生四烯酸、塞莱昔布、罗非昔布。 The Research Progress in Cyclooxygenase-2 And its Inhibitors liguojun Anhui University of Traditional Chinese MedicineABSTRACT Ring oxidase (Cyclooxygenase, COX), arachidonic acid (AA) converted to prostaglandins (PGs) enzyme important in the process of the speed limit. Its catalytic PGs in the body of a variety of physiological and pathological processes, such as inflammation，fever，the coagulation process. In 1991 confirmed that the ring oxidase (COX), there are two subtypes: COX -1 and cox-2, ring oxidase (COX) there are two kinds of isozymes involved in the synthesis of PG. Inducible enzyme of cox-2 in arthritis pain and inflammation，and COX enzyme - 1 with gastric and duodenal stomach protective of the involved in the synthesis of PG. Traditional NSAIDs such as aspirin，indomethacin and diclofenac, naproxen，etc to COXI and no selective COx2, can be called a nonselective COX inhibitors (Nomelective COX inhibitor). Its inhibition of COX2 is its foundation treatment, the inhibition of COX - I would become serious whole digestive tract damage. Some existing NSAIDs, low doses of C0X2