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机构地区:[1]中国医学科学院,中国协和医科大学药物研究所,北京100050
出 处:《药学学报》2000年第5期343-346,共4页Acta Pharmaceutica Sinica
摘 要:目的 建立COX1和COX2活性检测模型 ,为COX2选择性抑制剂的筛选及抗炎作用机制研究提供可靠方法。方法 COX1抑制剂筛选模型用新生小公牛主动脉内皮细胞为酶源 ,6 keto PGF1α的含量变化评价化合物对COX1的抑制作用。COX2抑制剂筛选模型用激活的小鼠腹腔巨噬细胞 ,PGE2 含量变化评价化合物对COX2的抑制作用。结果 Indomethacin可显著地抑制COX1的活性 ,Meloxicam可显著地抑制COX2的活性 ,其对COX2的选择性抑制作用高于前者。结论 COX1和COX2抑制剂筛选模型可用于COX2选择性抑制剂的筛选和机制研究。AIM To establish models of selective COX2 inhibitors which can help find selective COX2 inhibitors and study their mechanisms of antiinflammatory effects. METHODS The COX1 model was set up with cultured bovine arterial endothelial cells by detection of 6 keto PGF 1α in the supernatant of cultured cells. Three different COX2 models were set up with murine peritoneal macrophages. The COX2 activity of tested compounds were evaluated by the detection of PGE 2 production from AA in the supernatant of the murine macrophages stimulated with LPS or PMA. RESULTS Under the stimulation of LPS and PMA, the COX2 activities were markedly induced in a dose dependent manner. Indomethacin and meloxicam significantly inhibited COX1 activities with IC 50 of 2 7×10 -10 and 8 7×10 -8 mol·L -1 , respectively. Both of the above also greatly inhibited COX2 activities with IC 50 of 5 01×10 -10 and 2 86×10 -8 mol·L -1 , respectively. The ratios of IC 50COX1 /IC 50COX2 were 0 53 and 3 04, respectively. The results showed that indomethacin is a COX1 inhibitor, but meloxicam is a COX2 inhibitor. CONCLUSION The above three models for evaluation of COX1 and COX2 activities are effective, sensitive, simple, fast and accurate. They can be used for screening selective COX2 inhibitors and also provide a tool for studies of their mechanism of action of the antiinflammatory drugs.
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