血小板贮存损伤（PSL）主要由血小板活化和凋亡引起，是引起血小板贮存时间短、回输患者体内活力下降的主要原因，严重影响血小板输注效果甚至造成血小板输注无效，然而，离体贮存血小板发生活化和凋亡的机制目前未明。前期研究发现microRNALet7b在血小板贮存过程中表达发生明显改变，并可与血小板活性正相关的TLR43-UTR区结合调控其表达，提示microRNAsLet7b-TLR4通路可能在其中起重要作用。本课题拟进行以下研究：1）从血小板活化和凋亡两个方面，探讨microRNALet7b-TLR4及其下游调控通路引起PSL的分子机制；2）验证以microRNALet7b为作用靶点降低PSL的可行性；3）小鼠体内试验证实microRNALet7b-TLR4对贮存血小板活力及输注效果的影响。预期结果将有助于进一步认识血小板贮存损伤的发生机制，同时也将为研发新型血小板保存液提供实验基础和理论依据。

Platelet activation and apoptosis during storage caused platelet storage lesion (PSL),PSL shortened storage period and the survival of activated platelets after transfusion.However,platelet activation and apoptosis mechanisms in vitro are still unclear.Previous studies have found microRNALet7b ,associated with apoptosis,expression in platelet changed significantly during storage, which binds to platelet activitedrelatedfactors TLR4-UTR region and regulates its transcription. The results indicated microRNAsLet7b-TLR4 pathway may play an important role in PSL.So the project will try to 1)explain PSL mechanisms by microRNAsLet7b-TLR4 pathway from the point of view of platelet activation and apoptosis,2) test the feasibility of reducing PSL from regulating microRNAsLet7b expression, 3) demonstrate the effect of microRNA Let7b-TLR4 pathway on stored platelet transfusion effects in vivo. Expected results will contribute not only to a better understanding of the mechanism of PSL, but also provide experimental and theoretical basis for finding a new platelet storage solution.