线粒体ROS在血小板储存损伤中的作用及分子机制

血小板储存损伤（PSL）主要由血小板活化和凋亡引起，是引起血小板储存时间短、以及回输体内后活力下降的主要原因，然而，储存血小板如何引起活化和凋亡目前未明。申请人及其他研究者最近报道线粒体在血小板凋亡中起重要作用，提示线粒体可能参与引起PSL。申请人最新的研究发现，线粒体靶向的ROS拮抗剂，能改善22±2 C震荡保存的血小板质量、延缓PSL的发生；同时，采用能促进线粒体ROS产生的抗霉素A则加速PSL的发生，提示线粒体ROS可能在引起PSL中起重要作用。围绕这些发现，本课题拟进行以下研究：1）全面证实线粒体ROS在引起PSL中的作用；2）小鼠体内试验探明线粒体靶向的ROS拮抗剂对储存血小板体内活力的影响；3）从血小板活化和凋亡两个方面，探讨线粒体ROS引起PSL的分子机制。预期结果有助于进一步认识储存血小板发生活化和凋亡的分子机制，同时为研发新颖血小板保存液提供实验基础和理论依据。

Platelets are allowed to be kept for only 5 days because of platelet storage lesion (PSL), and the longer storage leads to decrease of platelets viability. PSL was mainly caused by the platelet activation and apoptosis. However, how platelets in storage trigger activation and apoptosis is currently unknown. Applicant and other researchers recently reported that mitochondria play a key role in platelet apoptosis, suggesting that mitochondria may be involved in causing PSL. Our latest study found that mitochondria-targeted antioxidant could improve the quality of platelet products stored in oscillation at RT. In addition, antimycin A, a complex III inhibitor which has been reported to promote mitochondrial ROS production, accelerated the occurrence of PSL, suggesting that mitochondrial ROS may be involved in triggering PSL. Focus on these findings, the aim of this study was to 1) confirm the role of mitochondrial ROS in PSL and 2) demonstrate whether mitochondria-targeted ROS antagonists could improve the viability of stored mice platelet products through in vivo experiments and 3) explore signaling pathway from mitochondrial ROS to PSL. Expected results will help to further understand the mechanism of platelet activation and apoptosis, and provide a experimental and theoretical basis for developing novel platelet preservation solution.