Liu Lei, Chen Mengxing, Zhao Lili, Zhao Qing, Hu Renping, Zhu Jie, Yan Rong, Dai Kesheng
Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, China.
Alcohol Clin Exp Res. 2017 Feb;41(2):291-298. doi: 10.1111/acer.13295. Epub 2017 Jan 12.
Alcohol abuse incurs severe medical conditions, such as thrombocytopenia and hemorrhage, but the pathogenesis is not totally understood. Alcohol has been reported to induce apoptosis in eukaryotic cells, such as hepatocyte, nerve cell, corneal fibroblasts. However, it is still unclear whether alcohol induces platelet apoptosis.
Washed human platelets were pretreated with ethanol (EtOH), and apoptotic events and platelet function were detected. In in vivo experiments, C57BL/6J mice were given EtOH by gavage. Platelet counts, tail bleeding time, and the stomach were examined.
EtOH dose dependently induces depolarization of mitochondrial inner transmembrane potential, up-regulation of Bax, down-regulation of Bcl-2, and caspase-3 activation. EtOH does not induce surface expression of P-selectin or PAC-1 binding, whereas significantly reduces collagen-, thrombin-, and ADP-induced platelet aggregation. Moreover, EtOH induces c-Jun NH2-terminal kinase activation. In an in vivo mouse model of the acute alcoholism, EtOH significantly reduces the number of circulating platelets, prolongs the tail bleeding time, and causes gastric mucosa hemorrhage.
These data demonstrate that EtOH induces mitochondria-mediated intrinsic platelet apoptosis, results in the reduction of the number of circulating platelets, and impairs in vivo hemostasis. These findings reveal the possible pathogenesis of hemorrhagic symptoms in patients experiencing acute alcohol intoxication.
酒精滥用会引发严重的医学病症，如血小板减少症和出血，但发病机制尚未完全明确。据报道，酒精可诱导真核细胞凋亡，如肝细胞、神经细胞、角膜成纤维细胞。然而，酒精是否会诱导血小板凋亡仍不清楚。
用乙醇（EtOH）预处理洗涤后的人血小板，并检测凋亡事件和血小板功能。在体内实验中，通过灌胃给予C57BL/6J小鼠EtOH。检测血小板计数、尾部出血时间，并检查胃部情况。
EtOH剂量依赖性地诱导线粒体内膜跨膜电位去极化、Bax上调、Bcl-2下调以及caspase-3激活。EtOH不会诱导P-选择素的表面表达或PAC-1结合，而会显著降低胶原蛋白、凝血酶和ADP诱导的血小板聚集。此外，EtOH会诱导c-Jun氨基末端激酶激活。在急性酒精中毒的体内小鼠模型中，EtOH显著减少循环血小板数量，延长尾部出血时间，并导致胃黏膜出血。
这些数据表明，EtOH诱导线粒体介导的内源性血小板凋亡，导致循环血小板数量减少，并损害体内止血功能。这些发现揭示了急性酒精中毒患者出血症状的可能发病机制。
