4.5 Article

Steroid Receptor Coactivator-3 Is Required for Inhibition of the Intestinal Muscularis Inflammatory Response of Postoperative Ileus in Mice

Journal

INFLAMMATION
Volume 44, Issue 3, Pages 1145-1159

Publisher

SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10753-020-01409-4

Keywords

inflammatory mechanisms; intestinal manipulation; knockout mice; postoperative ileus; steroid receptor coactivator-3

Funding

  1. National Natural Science Foundation of China [81601227, 81970462]
  2. Natural Science Foundation of Fujian Province [2016J05203, 2015J01548]
  3. Science and Technology Planning Projects of Xiamen Science & Technology Bureau [3502Z20154008]
  4. Science and Technology Planning Projects of Xiamen Health and Family Planning Commission [3502Z20149004]

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The study indicates that in a mouse model of postoperative ileus (POI), the expression of SRC-3 in the intestinal muscles may play a protective role. Proinflammatory cytokines, neutrophil numbers, and myeloperoxidase activity were significantly increased in KO mice compared to WT mice after intestinal manipulation.
Inflammation theory has suggested that the pathogenesis of postoperative ileus (POI) involves the steroid receptor coactivator-3 (SRC-3). Therefore, we investigated the role of SRC-3 in the muscles of the small intestine using a mouse POI model. Here, we reported that intestinal manipulation (IM) significantly reduced the extent of phenol red migration in the entire gastrointestinal tract, and the calculated geometric center (GC) value in wild-type (WT) mice at 24 h after surgery was higher than that in the knockout (KO) mice and in the sham-operated control group. The expression of SRC-3 was upregulated in the mouse intestinal muscularis at 24 h after surgical manipulation, and the mRNA and protein levels of inflammatory cytokines were upregulated compared with those in the control group. At 24 h after IM, the number of neutrophils in the experimental group was significantly higher than that in the control group; in the IM group, the number of neutrophils in the SRC-3(-/-) mice was markedly higher than that in the WT mice. At 24 h after IM, the myeloperoxidase (MPO) activity in the experimental group was significantly higher than that in the control group. In the IM group, the MPO activity of the SRC-3(-/-) mice was markedly higher than that of the WT mice. In summary, proinflammatory cytokines, the number of neutrophils, and the MPO activity were significantly increased in the muscularis of the jejunum and ileum of KO mice after IM compared with those of the WT mice, indicating that SRC-3 might play a protective role in POI.

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