Li Fengyang, Xu Dan, Hou Kai, Gou Xue, Li Yunman
State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
J Thromb Thrombolysis. 2020 Nov;50(4):874-885. doi: 10.1007/s11239-020-02098-4.
P2Y12 receptors on platelets have long been the main target of antiplatelet drugs. However, a growing number of studies have revealed that P2Y12 receptor activation on microglia and vascular smooth muscle cells (VSMCs) also aggravates ischemic stroke injury. The proliferation and migration of VSMCs in the vascular wall have important influence on the early lesion of atherosclerosis, which may lead to the origin of cerebral ischemic attack of atherosclerosis. Blockage of cellular P2Y12 receptors could inhibit microglial activation, block formation of platelet-leukocyte aggregates, reduce proinflammatory cytokine levels and suppress migration and proliferation of VSMCs, implying that apart from anti-thrombotic effect, P2Y12 inhibitors have additional neuroprotective, anti-inflammatory and anti-atherosclerotic therapeutic benefits against ischemic stroke. In this review, we will summarize recent advances in studies on P2Y12 receptors and emphatically introduce their significance in microglia, platelets and VSMCs after ischemic stroke, discussing how to exert the beneficial effects of P2Y12 inhibition.
血小板上的P2Y12受体长期以来一直是抗血小板药物的主要靶点。然而，越来越多的研究表明，小胶质细胞和血管平滑肌细胞（VSMC）上的P2Y12受体激活也会加重缺血性脑卒中损伤。血管壁中VSMC的增殖和迁移对动脉粥样硬化的早期病变有重要影响，这可能导致动脉粥样硬化性脑缺血发作的起源。阻断细胞P2Y12受体可抑制小胶质细胞激活，阻止血小板-白细胞聚集体的形成，降低促炎细胞因子水平，并抑制VSMC的迁移和增殖，这意味着除抗血栓作用外，P2Y12抑制剂对缺血性脑卒中还具有额外的神经保护、抗炎和抗动脉粥样硬化治疗益处。在本综述中，我们将总结P2Y12受体研究的最新进展，并着重介绍其在缺血性脑卒中后小胶质细胞、血小板和VSMC中的意义，探讨如何发挥P2Y12抑制的有益作用。
