Abstract
Background Chinese medicine decoction Da-Cheng-Qi-Tang (DCQT) is effective for treating gastrointestinal (GI) disorders, including postoperative ileus (POI); however, the mechanism by which DCQT improves intestinal motility of POI remains unknown. Purpose The aim of this study is to explore the therapeutic effect and mechanism of the decoction with the traditional formula DCQT (T-DCQT) and a modified DCQT (M-DCQT) in an experimental POI mouse model. Methods Mice were divided into 5 experimental groups with 16 mice per group as follows: (1) control group; (2) sham group; (3) POI group; (4) T-DCQT group and (5) M-DCQT group. Each group was subdivided into 2 groups in which the therapeutic effect was examined at 24h and 48h after operation. POI was induced by classic intestinal manipulation operation and the gastrointestinal(GI) motility was measured with a charcoal marking mixture gavage. The intestinal tissues were collected for evaluation of the histopathological alteration, and analysis of the expression of inflammatory signal pathways, as NF-κB, p38 MAPK, and TLR4 by qPCR, immunohistochemical staining and western-blotting, respectively. Plasma inflammatory cytokines were determined using a high-throughput liquid chip. All analyses were performed with samples collected 24 and/or 48h after operation. Results GI transit was significantly reduced in mice with POI and this dysfunction was alleviated after administration of either T-DCQT or M-DCQT enema. When compared to controls, the pathological changes in the ileum mucosal of POI mice were significantly improved, and the increased expression of NF-κB, p38 MAPK, and TLR4 in the intestinal tissues were reversed, following T- DCQT or M-DCQT treatment. Plasma inflammatory cytokines, such as IL-1α, IL-6, MCP-1, MIP-1β and IL-17 levels were significantly highly expressed in POI group, and most of them, as IL-1α, IL-6, MIP-1β and IL-17 were significantly reduced after T-DCQT or M-DCQT treatment. Conclusion The current study indicated that administration of T-DCQT or M-DCOT could ameliorate the POI-associated inflammatory response and improve GI motility, by controlling inflammatory cytokines release and modulating the expression of some inflammatory signal pathways in the POI mouse model.
Intestinal manipulation affects mucosal antimicrobial defense in a mouse model of postoperative ileus
