基于肠道生物标志物评价肠内营养补充益生菌治疗重症胰腺炎的获益与限制  

To evaluate the benefits and limitations of enteral nutrition supplementation with probiotics in the treat-ment of severe pancreatitis based on intestinal biomarkers

作　　者：许乐乐[1] 陈彦君[1] 陆件[2] 陈亚欧 XU Lele;CHEN Yanjun;LU Jian;CHEN Ya′ou(Department of Gastroenterology,the First Affiliated Hospital of Soochow University,Suzhou 215000,Jiangsu,China)

机构地区：[1]苏州大学附属第一医院消化内科,江苏苏州215000 [2]南京医科大学附属苏州医院(南京医科大学姑苏学院,苏州市立医院道前院区)重症医学科,江苏苏州215000

出　　处：《实用医学杂志》2024年第24期3458-3467,共10页The Journal of Practical Medicine

基　　金：国家自然科学基金项目(编号:82300595);南京医科大学姑苏学院科研项目(编号:GSKY20210215)。

摘　　要：目的通过肠型脂肪酸结合蛋白(I-FABP)、D-乳酸(D-Lac)、瓜氨酸的动态变化来协助评价肠内营养补充益生菌治疗重症胰腺炎的获益与限制。方法自2021年6月至2024年6月,共纳入苏州大学附属第一医院消化内科、南京医科大学附属苏州医院重症医学科重症胰腺炎病例153例,根据开始肠内营养(EN)后是否接受益生菌治疗分为研究组和对照组。研究组予双歧杆菌三联活菌胶囊每天4粒;观察期为EN后10 d,检测时间点:EN开始前(D0),EN开始第3天(D_(3)),EN开始第10天(D_(10))。3种肠道生物标志物(I-FABP、D-Lac、瓜氨酸)先采用重复测量方差分析和D_(10)为终点的疗效分析,并通过亚组分析探讨抗生素使用对益生菌的限制作用。比较两组胰腺炎常规评价指标(包括淀粉酶、炎症指标及相关评分等)、EN后肠道耐受性、90 d死亡率、出院时间等相关指标。结果重复测量方差分析结果显示益生菌干预下:(1)I-FABP主效应不显著(P=0.076),但与治疗时间交互效应显著(F=10.691,P=0.001,偏η^(2)=0.066);(2)D-Lac主效应不显著(P=0.761),与治疗时间交互效应同样不显著(F=0.004,P=0.995,偏η^(2)<0.001);(3)瓜氨酸主效应不显著(P=0.161),但与治疗时间交互效应显著(F=32.437,P<0.001,偏η^(2)=0.177)。终点疗效分析显示:(1)I-FABP研究组较对照组前下降水平更高[Difference in LS Mean(95%CI)=-0.43(-0.47~-0.40)μg/L,P<0.001];(2)D-Lac研究组较对照组前后差异无统计学意义[Difference in LS Mean(95%CI)=0.01(0.00~0.02)mmol/L,P=0.229],但亚组分析发现未使用抗生素者D-Lac下降水平表现为研究组低于对照组(P=0.043),抗生素使用与2组D-Lac下降水平有交互作用(P for interaction=0.012);(3)较对照组瓜氨酸在研究组上升水平更高(P<0.001)。两组胰腺炎常规评价指标、EN后肠道耐受性、90 d死亡率等差异无统计学意义(P>0.05);随访90 d,研究组较对照早期出院率更高(Breslow P=0.012)。结论基于症状缓解、Objective To assess the efficacy and limitations of enteral nutrition supplemented with probiotics in managing severe pancreatitis,we investigated the dynamic alterations of enteric fatty acid-binding protein(I-FABP),D-lactic acid(D-Lac),and citrulline.Methods Between June 2021 and June 2024,a total of 153 cases of severe pancreatitis were enrolled from the Department of Gastroenterology at the First Affiliated Hospital of Soochow University and the Department of Critical Care Medicine at Suzhou Hospital Affiliated with Nanjing Medical University.These cases were divided into two groups:A treatment group receiving probiotics in addition to enteral nutrition(EN),and a control group without probiotic supplementation.The treatment group received a daily dosage of four capsules containing bifidobacterium triple live bacteria.Intestinal biomarkers were assessed at three time points following EN initiation:before initiation(D_(0)),on day 3(D_(3)),and on day 10(D_(10))after initiation.Repeated measures ANOVA was employed to analyze the efficacy of the three intestinal biomarkers,with D_(10)as the endpoint for evaluation.Subgroup analysis was conducted to explore any potential influence of antibiotic usage on probiotic effects.Various conventional evaluation indicators for pancreatitis,including amylase levels,inflammation markers,relevant scores,post-EN intestinal tolerance,90-day mortality rates,discharge times,and other related outcomes were compared between the two groups.Results The results of a repeated measurement ANOVA showed that:(1)the main effect of I-FABP did not reach statistical significance(P=0.076),whereas the interaction effect was statistically significant(F=10.691,P=0.001,partialη^(2)=0.066);(2)Neither the main effect of D-Lac nor its interaction effect reached statistical significance(P=0.761 and P=0.995,respectively;F<0.004 for both effects,partialη^(2)<0.001);(3)Although the main effect of citrulline did not reach statistical significance(P=0.161),its interaction effect was found to be statistical

关 键 词：肠型脂肪酸结合蛋白 D-乳酸 瓜氨酸 重症胰腺炎 益生菌 

分 类 号：R576[医药卫生—消化系统]