全肠内营养对儿童克罗恩病肠道ACE1、ACE2表达的影响

Effect of exclusive enteral nutrition on the intestinal mucosal expression of ACE1 and ACE2 in children with Crohn’s disease

目的:比较克罗恩病(CD)患儿及正常儿童回肠末端肠黏膜中血管紧张素转换酶(ACE)1、ACE2表达差异及全肠内营养(EEN)对ACE1、ACE2表达的影响,探讨EEN诱导活动期CD缓解的机制。方法:纳入2020年9月至2021年12月于南京医科大学附属儿童医院消化科初次诊断并进行EEN治疗的轻中度CD患儿20例(CD组),记录患儿EEN治疗前后儿童CD活动指数评分(PCDAI)、CD简化内镜下评分(SES-CD)、实验室指标及营养指标。以同期因便血行肠镜检查确诊为结肠息肉的患儿为对照组,共20例。CD组及对照组患儿肠镜下取肠黏膜用实时荧光定量聚合酶链反应法及免疫荧光双染法测定ACE1、ACE2表达水平,CD患儿接受EEN治疗14周后再次检测肠黏膜中ACE1、ACE2表达水平。结果:CD组患儿EEN治疗14周后有效率为85%,治疗前CD患儿肠黏膜中ACE1、ACE1/ACE2表达高于对照组(P<0.05),治疗后与对照组比较,差异无统计学意义(P>0.05);CD组患儿治疗前ACE1水平与疾病活动度呈正相关(r=0.869 3,P<0.05)。结论:CD患儿存在ACE1和ACE2的失衡且ACE1轴的异常激活促进肠道炎症,EEN治疗可改善患儿临床症状及营养状况,并促进黏膜愈合,诱导CD缓解,可能与其可以改变肠黏膜中ACE1及ACE2的表达水平有关。

Objective: To compare the differences of angiotensin-converting enzyme(ACE)1 and ACE2 expression in the terminal ileal mucosa of children with Crohn’s disease(CD) and normal children, and to investigate the mechanism of exclusive enteral nutrition(EEN) to alleviate CD by investigating the effect of EEN on ACE1 and ACE2 expression. Methods: We selected patients with CD who were hospitalized from September 2020 to December 2021 in gastroenterology department of Children’s Hospital of Nanjing Medical University as CD group. Their clinical information including the pediatric Crohn’s disease activity index score(PCDAI), simplified endoscopic score of Crohn’s disease(SES-CD), laboratory indexes and nutritional status were collected before and after EEN treatment. Twenty children who visited for symptoms of blood in stool were diagnosed with colon polyps by colonoscopy in the same period as control group. Intestinal mucosal tissues were taken under colonoscopy for immunohistochemical detection of ACE1 and ACE2 protein expression and real-time quantitative polymerase chain reaction detection of ACE1 and ACE2 mRNA expression. The expression of ACE1 and ACE2 in the intestinal mucosa was measured again at 14 weeks after EEN treatment in CD group. Results: The clinical remission rate was 85% at 14 weeks after EEN treatment. The expression of ACE1 and ACE1/ACE2 of CD group before treatment was higher than those of control group(P<0.05), and no significant difference was found between the CD group after treatment and the control group(P>0.05). The ACE1 expression was positively correlated with disease activity in children in the CD group before treatment(r=0.869 3, P<0.05). Conclusion: In children with CD, there is an imbalance of ACE1 and ACE2 and abnormal activation of the ACE1 axis promotes intestinal inflammation. EEN was efficacious in the treatment of children with CD, inducing clinical remission, improving nutritional status and intestinal mucosal repair, which may be related to its ability to alter the expression of ACE1 and ACE2 in the intestinal mucosa.