粪便HMGB1、AI-2和HBD2在新生儿坏死性小肠结肠炎中的临床意义及与肠道菌群的关系

目的探讨粪便高迁移率族蛋白B1(HMGB1)、自诱导分子-2(AI-2)和人β-防御素2(HBD2)在新生儿坏死性小肠结肠炎(NEC)中的临床意义及其与肠道菌群的关系。方法选取2017年9月至2019年9月重庆市大渡口区人民医院收治的105例NEC患儿作为NEC组,以及同期出生的50例健康新生儿作为对照组。依据改良Bell-NEC分期标准将NEC患儿分为轻度NEC组及重度NEC组,根据病程分为急性期和恢复期,根据肠道菌群紊乱程度分为Ⅰ度失调组、Ⅱ度失调组及Ⅲ度失调组。检测受试新生儿粪便HMGB1、AI-2和HBD2水平,比较对照组和不同严重程度、不同NEC时期、不同肠道菌群紊乱程度的NEC患儿HMGB1、AI-2和HBD2水平。采用Spearman相关分析HMGB1、AI-2、HBD2水平与急性期NEC病情严重程度、肠道菌群紊乱程度的相关性。结果轻度NEC组和重度NEC组粪便HMGB1水平均高于对照组,且重度NEC组高于轻度NEC组(P<0.05);轻度NEC组和重度NEC组粪便AI-2和HBD2水平均低于对照组,且重度NEC组低于轻NEC度组(P<0.05)。粪便HMGB1水平与NEC病情严重程度呈正相关(r=0.412,P<0.05),AI-2和HBD2水平均与NEC病情严重程度均呈负相关(r=-0.405、-0.381,P<0.05)。NEC急性期和恢复期粪便HMGB1水平均高于对照组,且急性期高于恢复期(P<0.05);急性期粪便AI-2水平低于对照组和恢复期,且恢复期高于对照组(P<0.05);急性期和恢复期粪便HBD2水平均低于对照组,且恢复期高于急性期(P<0.05)。对照组粪便HMGB1水平<Ⅰ度失调组<Ⅱ度失调组<Ⅲ度失调组(P<0.05),而对照组粪便AI-2和HBD2水平>Ⅰ度失调组>Ⅱ度失调组>Ⅲ度失调组(P<0.05);粪便HMGB1水平与肠道菌群紊乱程度呈正相关(r=0.368,P<0.05),AI-2和HBD2水平与肠道菌群紊乱程度均呈负相关(r=-0.432、-0.406,P<0.05)。结论粪便中HMGB1、HBD2和AI-2水平与NEC的病情严重程度有关,并可以反映肠道菌群紊乱情况,而HMGB1水平降低、HBD2和AI-2水平升高则预示着病情好转。

Clinical significance of fecal HMGB1,AI-2 and HBD2 in neonatal necrotizing enterocolitis and their relationship with intestinal flora

Objective To investigate the clinical significance of fecal high mobility group protein B1(HMGB1),autoinducible-2(AI-2)and human beta-defensin 2(HBD2)in neonatal necrotizing enterocolitis(NEC)and their relationship with the intestinal flora.Methods A total of 105 children with NEC admitted to Chongqing Dadukou People′s Hospital from September 2017 to September 2019 were selected as the NEC group,and 50 healthy newborns born during the same period were selected as the control group.According to the modified Bell-NEC staging standard,children with NEC were divided into mild NEC group and severe NEC group.According to the course of disease,they were divided into acute stage and recovery stage.According to the degree of intestinal flora disorder,they were divided into degreeⅠdisorder group and degreeⅡdisorder group and degreeⅢdisorder group.The levels of HMGB1,AI-2 and HBD2 in feces of newborns were detected,and the control group and the HMGB1,AI-2 and HBD2 levels of NEC children with different severities,different NEC stages and different intestinal flora disorders were compared.Spearman correlation was used to analyze the correlation between the levels of HMGB1,AI-2 and HBD2 and the severity of NEC and the disorder of intestinal flora in acute stage.Results The level of fecal HMGB1 in the mild NEC group and the severe NEC group was higher than that in the control group,and the level in the severe NEC group was higher than that in the mild NEC group(P<0.05).The levels of fecal AI-2 and HBD2 in the mild NEC group and the severe NEC group were lower than the levels in the control group,and the levels in the severe NEC group were lower than those in the mild NEC group(P<0.05).The level of fecal HMGB1 was positively correlated with the severity of NEC(r=0.412,P<0.05),and the levels of AI-2 and HBD2 were negatively correlated with the severity of NEC(r=-0.405,-0.381,P<0.05).The level of fecal HMGB1 in the acute stage and the recovery stage of NEC was higher than that in the control group,and the level in the acute stage was higher than that in the recovery stage(P<0.05);The level of fecal AI-2 in the acute stage was lower than that in the control and the recovery stage,and the level in the recovery stage was higher than that in the control group(P<0.05);The level of fecal HBD2 in the acute stage and the recovery stage was lower than that in control group,and the level in the recovery stage was higher than that in the acute stage(P<0.05).The level of fecal HMGB1 in the control group wasdegreeⅠdisorder group>degreeⅡdisorder group>degreeⅢdisorder group(P<0.05).The level of fecal HMGB1 was positively correlated with the degree of intestinal flora disorder(r=0.368,P<0.05),and the levels of AI-2 and HBD2 were negatively correlated with the degree of intestinal flora disorder(r=-0.432,-0.406,P<0.05).Conclusion The levels of HMGB1,HBD2 and AI-2 in feces are related to the severity of NEC and can reflect the disorder condition of intestinal flora.The decrease of HMGB1 level and the increase of HBD2 and AI-2 levels indicate the improvement of the condition.