胰腺坏死是重症急性胰腺炎（SAP）的重要并发症，研究表明SAP早期胰腺局部广泛微血栓形成是胰腺坏死发生的重要原因,而血管内皮细胞分泌的促血栓因子vWF可能参与其中，机制是募集血小板在血管损伤部位。我们前期研究发现：1）急性胰腺炎（AP）早期存在vWF的升高，且与病情严重程度和胰腺坏死有关；2）SAP小鼠外源性给予vWF清除蛋白ADAMTS13可减少胰腺微血栓，保护腺泡细胞。此外，有研究发现ADAMTS13具有血管内皮保护作用，其机制可能与RhoA/VEGF有关。据此我们假设：SAP早期ADAMTS13可以降低vWF的活性，保护血管内皮，从而减少胰腺微血栓形成，改善胰腺坏死。我们将1）探索AP患者早期vWF多聚体变化，分析与疾病预后尤其是胰腺坏死的关系；2）在SAP模型中，评估ADAMTS13缺失或高表达对胰腺微血管和坏死的影响；3）利用体内外实验探索ADAMTS13保护血管内皮的分子机制。

Pancreatic necrosis is an important complication of severe acute pancreatitis(SAP). Previous studies suggested that diffusive formation of microthrombi is an important cause of pancreatic necrosis and vWF, which is synthesized in the endothelial cells, may participate in the process by recruiting platelets at the injury site. Our previous study found that：1）vWF significantly increased in patients with acute pancreatitis(AP) and is associated with the severity of AP and pancreatic necrosis;2）In a rodent model of SAP, administration of ADAMTS13(cleaving protein of vWF) could inhabit formation of pancreatic microthrombi and protect pancreatic acinar cells. Besides, results from other studies indicated that ADAMTS13 could alleviate endothelial injury probably via the RhoA/VEGF pathway. According to the abovementioned results, we hypothesize that ADAMTS13 could lower the activity of vWF and protect impaired endothelial cells in pancreatic microvascular during SAP, therefore improve pancreatic necrosis by reducing formation of microthrombi. In the present study, we would 1)Evaluate the change of vWF multimer and its association with disease severity and pancreatic necrosis in AP patients; 2)Study the effect of the change of ADAMTS13 activity on pancreatic microvascular and pancreatic necrosis in a rodent model of SAP;3) Explore the mechanism regarding how ADAMTS13 alleviate the impairment of endothelial cells with both in vitro and in vivo experiments.