血小板活化是脓毒症时凝血系统激活过程中的重要事件，但其调控机制还未被清楚阐明。我们的前期研究首次证实脓毒症早期血小板关键激酶GSK-3β活性明显提高，与血小板活化关系密切，外源性CO干预GSK-3β活性被下调。我们进一步推测CO通过sGC/cGMP/GSK-3β途径调节血小板活化。本研究采用CLP脓毒症动物模型和相关血小板模型，以新型外源性CO干预，运用基因分析、蛋白质水平测定等手段，在分子、细胞和整体等不同层面上，研究sGC/cGMP/GSK-3β信号途径对血小板活化的调节作用，尤其是重要信号分子（Akt,PKG）活性变化对GSK-3β的动态调控，旨在探明脓毒症血小板sGC/cGMP/GSK-3β信号途径顺序活化与调节激酶之间的相关关系，发现或探明GSK-3β及重要激酶是否是CO的作用对象及机制，明确CO调节脓毒症时血小板异常活化及信号传导的（部分）分子学基础，为脓毒症的治疗提供新思路。

Activation of platelets played a major role in sepsis, but its mechnisms remain to be investigated. Our previous studies have shown that the activity of GSK-3β, a key ser-thr kinase, was increased strongly and was associated with overactivation of coagβulation system. We thus hypothesis that exogenous CO can regulate activation of platelets through sGC/cGMP/GSK-3βpathway. This project employs CLP mice and LPS-stimulated platelets as sepsis models to examine the dynamic state of sGC/cGMP/GSK-3βpathway , especially the phosphorylation level of GSK-3β, and its relative regulatory kinases under the intervention of the exogenous CO liberated by CO-releasing molecules. These important factors will be investigated in the molecular and cellular levels through applying updated molecular biological techniques including gene analysis, measurement of protein expressions. The dynamic changes of important kinases (Akt, PKG) phosphorylation will be further explored. Thus, this project focuses on the relationship between the modification of GSK-3 β, and its relative regulatory kinases phosphorylation and activity of platelets during sepsis. Furthermore, the effects of exogenous CO on regulating GSK-3β phosphorylation in sepsis and potential mechnisms will be evaluted in this project. Therefor, we are in attempt to find which kinds of phosphorylation regulatory factors will be the novel targets of exogenous CO, in order to elucidate molecular mechnisms (even partly) responsible for the regulatory effects of CO on abnormal activity of platelets and signal transduction during sepsis and to provide theoretical basis and new idea for the research and treatment of sepsis.