低温体外循环手术中会出现严重凝血功能障碍，既往研究对其机制，尤其是内源性凝血途径极少涉及。激肽释放酶/凝血因子XII通路是内源性凝血途径的始动通路。本课题组研究发现，凝血因子XII在低温体外循环围手术期受到明显抑制，程度远大于外源性凝血物质。据此我们提出假说：因低温抑制肝脏实质细胞分泌的激肽释放酶原及其活化产物激肽释放酶，导致凝血因子XII合成下降，进而引起凝血功能障碍。本课题拟在低温体外循环手术动物模型上，通过分组温度实验观察激肽释放酶/凝血因子XII通路在低温体外循环围手术期的变化规律，通过基因敲除小鼠实验及体外肝脏细胞原代培养探索激肽释放酶/凝血因子XII通路在低温下引发凝血功能障碍的作用机制，通过围术期补充激肽释放酶验证其纠正围手术期凝血功能障碍的效果，最终阐明激肽释放酶/凝血因子XII通路在低温体外循环凝血过程中的作用及机制，为低温体外循环手术中失血并发症的防治策略提供新靶点。

Severe coagulopathy can occur during the surgery with hypothermia and cardiopulmonary bypass, but very few previous studies explored the mechanism, especailly the intrinsic coagulation pathway. Kallikrein/coagulation factor XII pathway is considered as the initiating process of intrinsic pathway. The prior studies of our team found that coagulation factor XII underwent significant inhibition because of hypothermia and cardiopulmonary bypass during the perioperative period, with an inhibited trend far greater than the extrinsic clotting substances. Accordingly, we come up with the hypothesis that due to the process of hypothermia, the synthesis of prokallikrein and kallikrein in hepatic parenchymal cells are critically inhibited, results in decreased generation of coagulation factor XII and continuous coagulopathy. The study will be conducted in three aspects to verify the hypothesis above: Firstly, observe the changing trend of kallikrein/coagulation factor XII pathway in the hypothermia and cardiopulmonary bypass animal model; Secondly, explore the mechanism of coagulopathy during hypothermia and cardiopulmonary bypass caused by kallikrein/coagulation factor XII pathway, using the gene knockout mice hypothermic model in vivo and primary cells culture experiment in vitro; Thirdly, evaluate the effect of improving perioperative coagulation function by complementing exogenous kallikrein in animal surgical model. We expect to clarify the function and mechanism of kallikrein/coagulation factor XII pathway in coagulopathy during hypothermia and cardiopulmonary bypass, and provide new targets for preventing hemorrhagic complications during the perioperative period with the present project.