肝素结合蛋白在急性胰腺炎发展中的作用及初步机制研究  

The role and preliminary mechanism of Heparin-binding protein in the develoment of acute pancreatitis

作　　者：尹纯林[1] 王弦[2] 高明[1] 王琪 孙远松 李贺[1] Yin Chunlin;Wang Xian;Gao Ming;Wang Qi;Sun Yuansong;Li He(Department of Emergency Surgery,the Second Affiliated Hospital of Anhui Medical University,Hefei 230601,China;Department of Pathology,the Second Affiliated Hospital of Anhui Medical University,Hefei 230601,China)

机构地区：[1]安徽医科大学第二附属医院急诊外科,合肥230601 [2]安徽医科大学第二附属医院病理科,合肥230601

出　　处：《中华急诊医学杂志》2023年第2期230-235,共6页Chinese Journal of Emergency Medicine

基　　金：安徽省重点研究与开发计划项目(201904a07020066);安徽医科大学校基金(2021xkj178);中国初级卫生保健基金会液体治疗科研基金项目(YLGX-JZ-2020010)。

摘　　要：目的通过临床分析和大鼠急性胰腺炎模型,探讨肝素结合蛋白(HBP)在急性胰腺炎(AP)发展中的作用及初步机制。方法(1)临床研究:留取安徽医科大学第二附属医院2021年1月1日至12月31日收治的AP患者入院30 min内的血液标本,其中重症急性胰腺炎(SAP)和非重症急性胰腺炎(NSAP)各20例,应用酶联免疫吸附测定(ELISA)的方法检测HBP、黏结合蛋白多糖-1(syndecan-1)及透明质酸(HA)的水平,并计算入院后改良CT严重指数(MCTSI),另选取20例健康体检者作为对照(HC)。采用Spearman相关性分析法分析HBP与syndecan-1、HA和MCTSI之间的相关性,受试者工作特征曲线(ROC)评估HBP预测AP严重程度。(2)动物实验:采用L-精氨酸腹腔注射法制备急性胰腺炎大鼠模型,健康对照组(NC,n=8)、低分子肝素(LMWH)干预组(n=8)、急性胰腺炎组(AP,n=8),12 h后将大鼠安乐死,收集外周静脉血检测HBP、syndecan-1及HA的水平。取肺组织和胰腺组织观察病理损伤情况并在透视电镜下观察血管内皮细胞多糖包被损伤情况。结果AP组患者入院时HBP水平较HC组明显升高,且SAP组升高更为明显。相关性分析分析发现HBP与syndecan-1、HA及MCTSI呈正相关。动物研究发现AP组大鼠HBP、syndecan-1及HA的水平较NC组显著升高,经LMWH干预后HBP、syndecan-1及HA的水平较HC组下降明显,差异有统计学意义。胰腺病理评分显示AP组明显升高,透视电镜发现正常组大鼠血管多糖包被完整,AP组结构破坏严重,经LMWH干预后结构脱落、损伤现象明显减轻,差异有统计学意义。结论HBP可促进AP病情进展,与HBP造成内皮细胞多糖包被结构破坏,血管通透性增加有关。Objective To explore the role and preliminary mechanism of heparin-binding protein(HBP)in the development of acute pancreatitis(AP)through clinical analysis and animal models.Methods(1)Clinical research:Blood samples were collected from AP patients admitted to the Second Affiliated Hospital of Anhui Medical University from January 1 to December 31,2021 within 30 min of admission,including 20 patients with severe acute pancreatitis(SAP)and 20 patients with non-severe acute pancreatitis(NSAP).Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of HBP,syndecan-1 and hyaluronic acid(HA).Modified CT severity index(MCTSI),another 20 healthy volunteers were selected as controls(HC).Spearman correlation analysis was used to analyze the correlation between HBP and syndecan-1,HA and MCTSI.Receiver operating characteristic(ROC)curve was used to evaluate HBP to predict AP severity.(2)Animal experiment:The rat model of acute pancreatitis was prepared by intraperitoneal injection of L-arginine.In the normal control group(NC,n=8),the low molecular weight heparin(LMWH)intervention group(n=8),and the acute pancreatitis group(AP,n=8),the rats were euthanized 12 h later,and peripheral venous blood was collected to detect the levels of HBP,syndecan-1 and HA.Lung tissue and pancreas tissue were collected to observe the pathological damage,and the polysaccharide coating damage of vascular endothelial cells was observed under a fluoroscopy electron microscope.Results The level of HBP at admission was significantly higher in the AP group than in the HC group,and the increase in the SAP group was more obvious.Correlation analysis showed that HBP was positively correlated with syndecan-1,HA and MCTSI.Animal studies found that the levels of HBP,syndecan-1 and HA in the AP group were significantly higher than those in the NC group.The pancreatic pathological score showed that the AP group was significantly increased,and the fluoroscopy electron microscope showed that the vascular polysaccharide coating was complete in the

关 键 词：急性胰腺炎 肝素结合蛋白 黏结合蛋白多糖-1 透明质酸 血管渗漏 多糖包被 低分子肝素 

分 类 号：R576[医药卫生—消化系统]