BACKGROUND Acute pancreatitis(AP) is rapid-onset pancreatic inflammation that causes local and systemic inflammatory response syndrome(SIRS) with high morbidity and mortality, but no approved therapies are currently a...BACKGROUND Acute pancreatitis(AP) is rapid-onset pancreatic inflammation that causes local and systemic inflammatory response syndrome(SIRS) with high morbidity and mortality, but no approved therapies are currently available. P-selectin glycoprotein ligand 1(PSGL-1) is a transmembrane glycoprotein to initiate inflammatory responses. We hypothesized that PSGL-1 may be involved in the development of AP and would be a new target for the treatment of AP.AIM To investigate the role and mechanism of PSGL-1 in the development of AP.METHODS The PSGL-1 expression on leukocytes was detected in peripheral blood of AP patients and volunteers. Pancreatic injury, inflammatory cytokines expression, and inflammatory cell infiltration was measured in AP mouse models induced with PSGL-1 knockout(PSGL-1-/-) and wild-type(PSGL-1+/+) mice. Leukocyteendothelial cell adhesion was measured in a peripheral blood mononuclear cell(PBMC)-endothelial cell coculture system.RESULTS The expression of PSGL-1 on monocytes and neutrophils was significantly increased in AP patients. Compared with PSGL-1+/+ mice, PSGL-1-/-AP mice induced by caerulein exhibited lower serum amylase, less Interleukin-1 beta(IL-1 beta) and Interleukin-6(IL-6) expression, less neutrophil and macrophage infiltration, and reduced peripheral neutrophil and monocyte accounts. PSGL-1 deficiency alleviated leukocyte-endothelial cell adhesion via IL-6 but not IL-1 beta.CONCLUSION PSGL-1 deficiency effectively inhibits the development of AP by preventing leukocyte-endothelial cell adhesion via IL-6 stimulation and may become a potential therapeutic target for treating AP.展开更多
目的探讨心外科ICU患者术后感染血清降钙素原(PCT)、P-选择素糖蛋白配体1(PSGL-1)、可溶性细胞间粘附因子-1(sICAM-1)与心肌肌钙蛋白I(cTnⅠ)的变化及意义。方法选取本院2016年1月至2019年3月心外科ICU患者108例,根据术后是否发生感染...目的探讨心外科ICU患者术后感染血清降钙素原(PCT)、P-选择素糖蛋白配体1(PSGL-1)、可溶性细胞间粘附因子-1(sICAM-1)与心肌肌钙蛋白I(cTnⅠ)的变化及意义。方法选取本院2016年1月至2019年3月心外科ICU患者108例,根据术后是否发生感染分为感染组37例、未感染组71例,另选择同期健康体检者48例作为对照组。比较3组血清PCT、PSGL-1、sICAM-1、cTnⅠ水平,Logistic回归分析心外科ICU患者术后感染的影响因素,Pearson相关性分析血清PCT、PSGL-1、sICAM-1与cTnⅠ关联性,对比感染组不同预后患者血清PCT、PSGL-1、sICAM-1、cTnⅠ水平,受试者工作特征(ROC)曲线分析各血清因子对预后的预测价值,采用Kaplan-Meier曲线进行生存分析。结果感染组血清PCT、PSGL-1、sICAM-1、cTnⅠ水平高于未感染组、对照组差异有统计学意义(P<0.05);合并基础性疾病、血清PCT、PSGL-1、sICAM-1、cTnⅠ是心外科ICU患者发生术后感染的独立危险因素(P<0.05);血清PCT、PSGL-1、sICAM-1与cTnⅠ呈正相关(P<0.05);感染第3、5天生存者血清PCT、PSGL-1、sICAM-1、cTnⅠ水平低于死亡者(P<0.05);感染第5 d cTnⅠ预测心外科ICU患者术后感染预后的AUC值最大,为0.804;随访28 d,血清PCT、PSGL-1、sICAM-1、cTnⅠ低危组、高危组的生存曲线对比,差异有统计学意义(P<0.05)。结论心外科ICU患者术后感染会引起血清PCT、PSGL-1、sICAM-1、c TnI异常表达,且表达水平与感染发生发展及预后有一定相关性,临床可通过监测上述血清因子表达超早期予以干预治疗,以改善预后。展开更多
基金Supported by National Natural Science Foundation of China,No. 81670387,No. 31671440,and No. 81800402。
文摘BACKGROUND Acute pancreatitis(AP) is rapid-onset pancreatic inflammation that causes local and systemic inflammatory response syndrome(SIRS) with high morbidity and mortality, but no approved therapies are currently available. P-selectin glycoprotein ligand 1(PSGL-1) is a transmembrane glycoprotein to initiate inflammatory responses. We hypothesized that PSGL-1 may be involved in the development of AP and would be a new target for the treatment of AP.AIM To investigate the role and mechanism of PSGL-1 in the development of AP.METHODS The PSGL-1 expression on leukocytes was detected in peripheral blood of AP patients and volunteers. Pancreatic injury, inflammatory cytokines expression, and inflammatory cell infiltration was measured in AP mouse models induced with PSGL-1 knockout(PSGL-1-/-) and wild-type(PSGL-1+/+) mice. Leukocyteendothelial cell adhesion was measured in a peripheral blood mononuclear cell(PBMC)-endothelial cell coculture system.RESULTS The expression of PSGL-1 on monocytes and neutrophils was significantly increased in AP patients. Compared with PSGL-1+/+ mice, PSGL-1-/-AP mice induced by caerulein exhibited lower serum amylase, less Interleukin-1 beta(IL-1 beta) and Interleukin-6(IL-6) expression, less neutrophil and macrophage infiltration, and reduced peripheral neutrophil and monocyte accounts. PSGL-1 deficiency alleviated leukocyte-endothelial cell adhesion via IL-6 but not IL-1 beta.CONCLUSION PSGL-1 deficiency effectively inhibits the development of AP by preventing leukocyte-endothelial cell adhesion via IL-6 stimulation and may become a potential therapeutic target for treating AP.
文摘目的探讨心外科ICU患者术后感染血清降钙素原(PCT)、P-选择素糖蛋白配体1(PSGL-1)、可溶性细胞间粘附因子-1(sICAM-1)与心肌肌钙蛋白I(cTnⅠ)的变化及意义。方法选取本院2016年1月至2019年3月心外科ICU患者108例,根据术后是否发生感染分为感染组37例、未感染组71例,另选择同期健康体检者48例作为对照组。比较3组血清PCT、PSGL-1、sICAM-1、cTnⅠ水平,Logistic回归分析心外科ICU患者术后感染的影响因素,Pearson相关性分析血清PCT、PSGL-1、sICAM-1与cTnⅠ关联性,对比感染组不同预后患者血清PCT、PSGL-1、sICAM-1、cTnⅠ水平,受试者工作特征(ROC)曲线分析各血清因子对预后的预测价值,采用Kaplan-Meier曲线进行生存分析。结果感染组血清PCT、PSGL-1、sICAM-1、cTnⅠ水平高于未感染组、对照组差异有统计学意义(P<0.05);合并基础性疾病、血清PCT、PSGL-1、sICAM-1、cTnⅠ是心外科ICU患者发生术后感染的独立危险因素(P<0.05);血清PCT、PSGL-1、sICAM-1与cTnⅠ呈正相关(P<0.05);感染第3、5天生存者血清PCT、PSGL-1、sICAM-1、cTnⅠ水平低于死亡者(P<0.05);感染第5 d cTnⅠ预测心外科ICU患者术后感染预后的AUC值最大,为0.804;随访28 d,血清PCT、PSGL-1、sICAM-1、cTnⅠ低危组、高危组的生存曲线对比,差异有统计学意义(P<0.05)。结论心外科ICU患者术后感染会引起血清PCT、PSGL-1、sICAM-1、c TnI异常表达,且表达水平与感染发生发展及预后有一定相关性,临床可通过监测上述血清因子表达超早期予以干预治疗,以改善预后。
