重症急性胰腺炎（SAP）是临床常见的危重疾病，严重威胁人类的生命安全,主要原因是并发严重的脓毒血症和多脏器功能不全(MODS)。小肠是最早受累的脏器，其根本原因是小肠微血管内皮细胞损伤致微循环障碍，导致小肠功能受损，尤其是粘膜屏障功能破坏，肠道细菌移位引起脓毒血症和多脏器功能不全。因此，对小肠血管内皮细胞损伤机制的探索已成为研究热点。我们前期研究发现糖萼（glycocalyx）的破坏和新近研究认为钙粘蛋白（VE-cadherin）内陷可以导致内皮细胞损伤，同时我们也发现髓性分化因子88（Myd88）介导的信号传导通路可能参与糖萼和钙粘蛋白的破坏，本研究计划以Myd88作为突破点，采用内皮细胞Myd88条件性基因敲除技术，分析糖萼和钙粘蛋白破坏在小肠微循环障碍中的意义及分子生物学机制，为今后开发以Myd88为靶标，以改善小肠微循环和小肠功能为目的的新型治疗措施提供理论依据。

Severe acute pancreatitis (SAP) is a critical illness, has been considered as the major cause of death with sepsis and multiple organ dysfunction (MODS). Small intestine is often most vulnerable, and microcirculatory dysfunction caused by vascular endothelial cell injury is an important reason leading to intestine injury, especially the mucosal barrier function damage. The mechanism of vascular endothelial cell injury of small intestine has been regarded as a hotspot. The glycocalyx, known as endothelial protective layer, and vascular endothelial-cadherin (VE-cadherin) maintain the stability of vascular permeability. The damage of glycocalyx and VE-cadherin were involved in vascular endothelial cell injury. Recent studies found that the myeloid differentiation factor 88 (Myd88)-mediated signal transduction may play an important role in the destruction of the glycocalyx and VE-cadherin. Therefore we will focus on the role of Myd88 in the mechanism of vascular endothelial cell injury, by using the conditional knock-out Myd88 method, and analyze glycocalyx and VE-cadherin’s change of small intestine vascular endothelial cell caused by AP, which will help us to develop a new theoretical treatment on microcirculatory dysfunction.