血清HMGB1、TLR9与急性胰腺炎肠粘膜屏障损伤的关系

Relationships between serum HMGB1,TLR9 and intestinal mucosal barrier damage in acute pancreatitis

目的探讨血清高迁移率族蛋白B1(HMGB1)、Toll样受体9(TLR9)与急性胰腺炎(AP)肠粘膜屏障损伤的关系。方法选取2017年9月-2018年5月广元市中医医院收治的84例AP患者为观察组,按疾病严重程度将其分为重症急性胰腺炎(SAP)组23例、中度重症急性胰腺炎(MSAP)组32例及轻型急性胰腺炎(MAP)组29例,同期选择56名健康体检者为对照组。采用ELISA法检测血清HMGB1、TLR9、二胺氧化酶(DAO)水平,采用鲎试剂比浊检测内毒素(LPS)水平,采用酶学分光光度法检测血清D-乳酸水平,采用离子色谱法检测尿乳果糖和甘露醇比值(L/M)。采用Pearson相关分析法分析血清HMGB1、TLR9水平与肠黏膜损伤指标的关系。采用ROC曲线分析血清HMGB1、TLR9对AP患者肠黏膜损伤的诊断价值。结果观察组患者24、48、72 h时D-乳酸、LPS、DAO、尿L/M水平显著高于对照组(P<0.05);观察组患者24、48、72 h时血清HMGB1、TLR9表达水平显著高于对照组(P<0.05);SAP组患者24、48、72 h时血清HMGB1、TLR9表达水平显著高于MSAP组、MAP组(P<0.05),且MSAP组患者较MAP组高(P<0.05);发病后24 h时,AP患者血清HMGB1、TLR9表达水平与肠黏膜损伤指标D-乳酸、LPS、DAO、尿L/M呈正相关(P<0.05);血清HMGB1、TLR9及HMGB1+TLR9联合诊断发病后24 h时AP患者肠黏膜损伤的曲线下面积分别为0.824、0.731、0.866,敏感度分别为90.00%、51.70%、88.30%,特异度分别为71.10%、86.80%、76.30%。结论 AP患者血清中HMGB1、TLR9表达水平上调,其水平升高可能与肠粘膜屏障损伤有关,可作为判断AP患者肠粘膜屏障损伤的参考指标。

Objective To investigate the relationships between serum high mobility group protein B1(HMGB1),Toll-like receptor 9(TLR9)and intestinal mucosal barrier damage in acute pancreatitis(AP).Methods 84 patients with AP admitted to Guangyuan Hospital of Traditional Chinese Medicine from September 2017 to May 2018 were selected as the study group,they were divided into severe acute pancreatitis(SAP)group,moderate severe acute pancreatitis(MSAP)group and mild acute pancreatitis(MAP)group according to the severity of the disease;56 healthy persons were selected as control group during the same period.Levels of serum HMGB1,TLR9 and diamine oxidase(DAO)were measured by ELISA method;the level of endotoxin(LPS)was determined by tachypleus amebocyte lysate turbidimetry.Serum D-lactic acid level was determined by enzymological spectrophotometry,and urinary lactulose/mannitol ratio(L/M)was determined by ion chromatography.Pearson correlation analysis was used to analyze the relationships between serum HMGB1 and TLR9 levels with intestinal mucosal injury index.The diagnostic values of serum HMGB1 and TLR9 for intestinal mucosal injury in patients with AP were analyzed by ROC curve.Results The levels of D-lactic acid,LPS,DAO and urinary L/M in the observation group were significantly higher than those in the control group at 24,48 and 72 h(P<0.05);the levels of serum HMGB1 and TLR9 in the observation group were significantly higher than those in the control group at 24,48 and 72 h(P<0.05);the levels of serum HMGB1 and TLR9 in SAP group were significantly higher than those in MSAP group and MAP group at 24,48 and 72 h(P<0.05);the MSAP group was higher than the MAP group(P<0.05);at 24 h after onset,serum HMGB1 and TLR9 levels in patients with AP were positively correlated with intestinal mucosal injury indicators Dlactic acid,LPS,DAO and urinary L/M(P<0.05);the areas under the curve of serum HMGB1,TLR9 levels and HMGB1+TLR9 detections in the diagnosis of intestinal mucosal injury in patients with AP at 24 h after onset were 0.824,0.731 and0.866,respectively;the sensitivities were 90.00%,51.70%and 88.30%,respectively,the specificities were 71.10%,86.80%and 76.30%,respectively.Conclusion The expression levels of HMGB1 and TLR9 in serum of patients with AP were up-regulated,which might be related to the damage of intestinal mucosal barrier,and could serve as reference indexes for judging the damage of intestinal mucosal barrier in patients with AP.