Sheu J R, Hung W C, Su C H, Lin C H, Lee L W, Lee Y M, Yen M H
Graduate Institute of Medical Sciences, Taipei Medical College, Taiwan.
Eur J Haematol. 1999 May;62(5):317-26. doi: 10.1111/j.1600-0609.1999.tb01909.x.
In this study, Escherichia coli LPS dose-dependently (100-500 microg/ml) and time-dependently (10-60 min) inhibited platelet aggregation in human and rabbit platelets stimulated by agonists. LPS also dose-dependently inhibited the intracellular Ca2+ mobilization in human platelets stimulated by collagen. In addition, LPS (200 and 500 microg/ml) significantly increased the formation of cyclic GMP but not cyclic AMP in platelets. LPS (200 microg/ml) significantly increased the production of nitrate within a 10-min incubation period. Furthermore, LPS also dose-dependently inhibited platelet aggregation induced by PDBu (30 nmol/l), a protein kinase C activator. These results indicate that the antiplatelet activity of E. coli LPS may be involved in the activation of a nitric oxide/cyclic GMP pathway in platelets, resulting in inhibition of platelet aggregation. Therefore, LPS-mediated alteration of platelet function may contribute to bleeding diathesis in septicemic and endotoxemic patients.
在本研究中，大肠杆菌脂多糖（LPS）以剂量依赖性方式（100 - 500微克/毫升）和时间依赖性方式（10 - 60分钟）抑制激动剂刺激的人及兔血小板的聚集。LPS还以剂量依赖性方式抑制胶原蛋白刺激的人血小板内的Ca2+动员。此外，LPS（200和500微克/毫升）显著增加血小板中环鸟苷酸（cGMP）的形成，但不增加环磷酸腺苷（cAMP）的形成。LPS（200微克/毫升）在10分钟的孵育期内显著增加硝酸盐的产生。此外，LPS还以剂量依赖性方式抑制蛋白激酶C激活剂佛波酯（PDBu，30纳摩尔/升）诱导的血小板聚集。这些结果表明，大肠杆菌LPS的抗血小板活性可能与血小板中一氧化氮/环鸟苷酸途径的激活有关，从而导致血小板聚集的抑制。因此，LPS介导的血小板功能改变可能导致败血症和内毒素血症患者的出血倾向。
