PDF(Pubmed)
Abstract：
Clinically, indobufen is widely used for the treatment of antiplatelet aggregation and anticoagulation. Prior studies have discovered that abnormal platelet function can be promptly restored to normal when the drug is stopped. Herein, through the study of the enzyme reaction kinetics, we demonstrated that the inhibitory effect of indobufen on cyclooxygenase-1 (COX-1) was reversible and non-competitive. Specifically, the cyclooxygenase inhibition experiment showed that the level of 6-keto-PGF1α in the gastric mucosa of the indobufen-treated groups was significantly higher than that of the aspirin group (###p < 0.001), indicating a higher level of PGI2 in and a better physiological state of the gastric mucosa. Moreover, the rat gastric ulcer index and mucosal section experiments further confirmed the relief of gastrointestinal irritation and the adverse reaction rate of the indobufen-treated group compared to those of the aspirin group. Furthermore, indobufen was verified to exert reversible inhibitory activity on the heme group of COX-1 and thus reversibly inhibit COX-1 activity. In general, compared with aspirin, the long-term oral administration of indobufen yields a lower risk of gastrointestinal symptoms, such as ulcers.
摘要：
临床上,吲哚布芬广泛用于抗血小板聚集和抗凝治疗。先前的研究发现，当停药时，异常的血小板功能可以迅速恢复正常。在这里，通过对酶反应动力学的研究,我们证明吲哚布芬对环氧合酶-1（COX-1）的抑制作用是可逆的和非竞争性的。具体来说,环氧合酶抑制实验表明，吲哚布芬治疗组胃粘膜中6-酮-PGF1α的水平明显高于阿司匹林组（##p<0.001），表明胃粘膜的PGI2水平较高，生理状态较好。此外，大鼠胃溃疡指数和粘膜切片实验进一步证实，与阿司匹林组相比，吲哚布芬治疗组的胃肠道刺激减轻和不良反应发生率降低。此外，证实吲哚布芬对COX-1的血红素组具有可逆的抑制活性，从而可逆地抑制COX-1活性。总的来说,与阿司匹林相比，长期口服吲哚布芬可以降低胃肠道症状的风险，如溃疡。
