[肠道微生物群稳态对坏死性小肠结肠炎新生大鼠模型造血的影响]

[Effect of gut microbiota homeostasis on hematopoiesis in a neonatal rat model of necrotizing enterocolitis].

作者信息

Wang Shan-Shan, Cai Jin-Yang, Shi Ai-Wu, Cao Yan

机构信息

Medical Research Center, Women's Hospital of Nanjing Medical University/Nanjing Maternity and Child Health Care Hospital, Nanjing 210004, China.

出版信息

Zhongguo Dang Dai Er Ke Za Zhi. 2023 Aug 15;25(8):855-863. doi: 10.7499/j.issn.1008-8830.2301082.

DOI:10.7499/j.issn.1008-8830.2301082

PMID:37668035

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10484087/

Abstract

OBJECTIVES

To study the effect of gut microbiota on hematopoiesis in a neonatal rat model of necrotizing enterocolitis (NEC).

METHODS

Neonatal Sprague-Dawley rats were randomly divided into a control group and a model group (NEC group), with 6 rats in each group. Formula milk combined with hypoxia and cold stimulation was used to establish a neonatal rat model of NEC. Hematoxylin and eosin staining was used to observe the pathological changes of intestinal tissue and hematopoiesis-related organs. Routine blood tests were conducted for each group. Immunohistochemistry was used to observe the changes in specific cells in hematopoiesis-related organs. Flow cytometry was used to measure the changes in specific cells in bone marrow. 16S rDNA sequencing was used to observe the composition and abundance of gut microbiota.

RESULTS

Compared with the control group, the NEC group had intestinal congestion and necrosis, damage, atrophy, and shedding of intestinal villi, and a significant increase in NEC histological score. Compared with the control group, the NEC group had significantly lower numbers of peripheral blood leukocytes and lymphocytes (<0.05), nucleated cells in the spleen, thymus, and bone marrow, and small cell aggregates with basophilic nuclei in the liver (<0.05). The NEC group had significant reductions in CD71 erythroid progenitor cells in the liver, CD45 lymphocytes in the spleen and bone marrow, CD3 T lymphocytes in thymus, and the proportion of CD45CD3CD43SSC neutrophils in bone marrow (<0.05). There was a significant difference in the composition of gut microbiota between the NEC and control groups, and the NEC group had a significant reduction in the abundance of and a significant increase in the abundance of - (<0.05), which replaced and became the dominant flora.

CONCLUSIONS

Multi-lineage hematopoietic disorder may be observed in a neonatal rat model of NEC, which may be associated with gut microbiota dysbiosis and abnormal multiplication of the pathogenic bacteria -.

摘要

目的

在坏死性小肠结肠炎（NEC）新生大鼠模型中研究肠道微生物群对造血的影响。

方法

将新生Sprague-Dawley大鼠随机分为对照组和模型组（NEC组），每组6只。采用配方奶联合缺氧和冷刺激建立新生大鼠NEC模型。苏木精-伊红染色观察肠道组织及造血相关器官的病理变化。对每组进行血常规检测。免疫组织化学观察造血相关器官中特定细胞的变化。流式细胞术检测骨髓中特定细胞的变化。采用16S rDNA测序观察肠道微生物群的组成和丰度。

结果

与对照组相比，NEC组出现肠道充血、坏死，肠绒毛损伤、萎缩和脱落，NEC组织学评分显著升高。与对照组相比，NEC组外周血白细胞和淋巴细胞数量显著降低（<0.05），脾脏、胸腺和骨髓中的有核细胞以及肝脏中嗜碱性核的小细胞聚集物数量显著降低（<0.05）。NEC组肝脏中CD71红系祖细胞、脾脏和骨髓中CD45淋巴细胞、胸腺中CD3 T淋巴细胞以及骨髓中CD45CD3CD43SSC中性粒细胞的比例显著降低（<0.05）。NEC组与对照组肠道微生物群组成存在显著差异，NEC组丰度显著降低，丰度显著升高（<0.05），取代成为优势菌群。