重症急性胰腺炎患者肠黏膜屏障损伤与血清二胺氧化酶和TLR9水平及肠道菌群和其代谢产物的相关性

Relationship between intestinal mucosal barrier injury and levels of serum diamine oxidase and TLR9,intestinal flora and its metabolites in severe acute pancreatitis

目的探究重症急性胰腺炎患者肠黏膜屏障损伤与血清二胺氧化酶(DAO)、Toll样受体9(TLR9)水平及肠道菌群和其代谢产物的相关性,为该类患者的治疗提供参考。方法选取2020年1月至2022年1月在我院进行诊疗的急性胰腺炎患者107例为研究组,根据其病情严重程度将其分为轻中症组(n=51)和重症组(n=56)。另选同期50例在我院进行健康体检的志愿者纳入对照组。比较各组对象不同时间点的血清DAO和TLR9水平、肠黏膜屏障损伤指标(内毒素、D-乳酸、乳果糖/甘露醇比值)、肠道菌群情况及肠道菌群代谢产物水平。结果与对照相比较,研究组患者的血清DAO、TLR9、内毒素、D-乳酸水平和乳果糖/甘露醇比值以及肠道肠球菌、酵母菌数量均显著升高,肠道双歧杆菌、消化球菌、乳杆菌数量以及丙酸、丁酸、乙酸水平均显著降低(均P<0.05)。重症组和轻中症组患者入院24 h、48 h、72 h时的血清DAO、TLR9水平呈现为先升高后降低的趋势,且重症组患者各时间点的血清DAO、TLR9水平均高于轻中症组(均P<0.05)。重症组和轻中症组患者入院24 h、48 h、72 h时的内毒素、D-乳酸水平及乳果糖/甘露醇比值均呈现先升高后降低的趋势,且重症组患者各时间点的内毒素、D-乳酸水平及乳果糖/甘露醇比值均高于轻中症组(均P<0.05)。患者内毒素水平与DAO、TLR9水平、双歧杆菌、消化球菌、乳杆菌、乙酸、丁酸水平均呈正相关(均P<0.05),与肠球菌、酵母菌数量均呈负相关(均P<0.05),与丙酸水平无显著相关性(P>0.05)。患者D-乳酸水平与双歧杆菌、消化球菌、乳杆菌、乙酸、丁酸、肠球菌、酵母菌水平均无显著相关性(P>0.05),与DAO、TLR9、丙酸水平均呈正相关(均P<0.05)。乳果糖/甘露醇比值与双歧杆菌、消化球菌、乳杆菌、乙酸水平均呈负相关(均P<0.05),与DAO、TLR9、酵母菌、丁酸水平均呈正相关(均P<0.05),与丙酸水平无显著相关性(P>0.05)。结论重症急性胰腺炎患者肠黏膜屏障损伤更重,血清DAO、TLR9、内毒素、D-乳酸水平及乳果糖/甘露醇比值均显著升高,同时患者的肠黏膜屏障损伤程度与其血清DAO、TLR9水平、肠道菌群数量及代谢产物水平具有相关性。

Objective To explore the relationship of intestinal mucosal barrier damage with the levels of serum diamine oxidase(DAO)and toll-like receptor 9(TLR9),intestinal flora and their metabolites in severe acute pancreatitis(AP),providing a reference for the treatment.Methods A total of 107 patients with AP who underwent diagnosis and treatment in our hospital from January 2020 to January 2022 were selected as the research group,and further divided into mild/moderate disease group(n=51)and severe disease group(n=56)based on their severity.Another 50 volunteers who underwent health examinations in our hospital were selected as the control group.The serum levels of DAO and TLR9,intestinal mu-cosal barrier damage indicators(endotoxin,D-lactic acid,Lactulose/Mannitol ratio),intestinal flora and intestinal metabolite levels at different time points were compared between groups.Results Compared with the control group,the levels of serum DAO,TLR9,endotoxin and D-lactic acid,Lactulose/Mannitol ratio,and counts of Enterococcus and yeast in the research group increased,while the levels of Bifidobacteria,Peptococcus,Lactobacillus,propionic acid,butyric acid,and acetic acid decreased(all P<0.05).The levels of DAO and TLR9 in the severe and mild/moderate disease groups showed a trend of first increasing and then decreasing at 24,48,and 72 hours of admission,and the levels of DAO and TLR9 in the severe disease group were higher than those in the mild/moderate disease group at all time points(all P<0.05).The levels of endotoxin and D-lactic acid,Lactulose/Mannitol ratio in severe disease group and mild/moderate disease group showed a trend of first increasing and then decreasing at 24,48,and 72 hours of admissiona,and those in severe disease group at each time point were higher than those in mild/moderate disease group respectively(all P<0.05).The levels of endotoxin in patients was positively correlated with the levels of DAO,TLR9,Bifidobacteria,Enterococcus,Lactobacillus,acetic acid and butyric acid,while negatively correlated with the levels of Enterococcus and yeast,but had no significant correlation with the level of propionic acid.The level of D-lactic acid had no significant correlation with the levels of Bifidobacteria,Peptococcus,Lactobacillus,acetic acid,butyric acid,Enterococcus,and yeast,but was positively correlated with the levels of DAO,TLR9 and propionic acid.The ratio of Lactulose/Mannitol was negatively correlated with the levels of Bifidobacteria,Enterococcus,Lactobacillus and acetic acid,while positively correlated with the levels of DAO,TLR9,yeast and butyric acid,but had no significant correlation with the level of propionic acid.Conclusion The intestinal mucosal barrier damage was more severe in patients with severe acute pancreatitis,and the levels of serum DAO,TLR9,endotoxin,D-lactic acid and Lactulose/Mannitol ratio significantly increased.The intestinal mucosal barrier injury of patients was correlated with the levels of serum DAO,TLR9,intestinal flora and its metabolites.