Effect And Mechanism Of Modified Da-Cheng-Qi-Tang On The Gastrointestinal Motility In Mouse With Postoperative Ileus

Objective:The pathogenesis of postoperativeileus(POI)is far fromelucidated,and its clinical prevention and treatment are still being explored.Chinese medicine decoction Da-Cheng-Qi-Tang(DCQT)is effective for treating gastrointestinal(GI)disorders,like POI,but the mechanism that how DCQT improves GI motility during POI remains unknown.The aim of this study is to explore the therapeutic effects and mechanism of traditional formula DCQT(T-DCQT)and modified DCQT(M-DCQT)on experimental POI mouse model.Methods:Eighty mice were divided equally into 5 experimental groups: control group,sham group,POI group,T-DCQT group and M-DCQT group.Each group was further subdivided into treated and mock-treatedgroups(n=8 in each group).Therapeutic effect was examined at 24 h and 48 h after operation.POI was induced by classic intestinal manipulation and the gastrointestinal(GI)motility was measured with charcoal marking gavage.The intestinal tissues were collected for evaluation of histopathological alterations and expression of inflammatory signal molecules including NF-κB,p38 MAPK,and TLR4 by q RT-PCR,immunohistochemical staining and westernblotting,respectively.Plasma inflammatory cytokines were also determined using high-throughput liquid chip.All analyses were performed with samples collected at 24 h and/or 48 h after operation.Results:GI motility was significantly reduced in mice with POI and this dysfunction was alleviated after administration of either T-DCQT or M-DCQT enema(p<0.05 or p<0.01).Compared with control group,POI mice showed congestion and edema in the intestinal mucosa,and increased levels of expression of NF-κB,p38 MAPK,and TLR4 in the intestinal tissues(p<0.05 or p<0.01).T-DCQT or M-DCQT treatment ameliorated these changes in POI mice.Plasma levels of pro-inflammatory cytokines,such as IL-1α,IL-6,MCP-1,MIP-1β and IL-17 were significantly increased in POI group(p<0.05 or p<0.01),which were all significantly reduced following T-DCQT or M-DCQT treatment.Conclusion:T-DCQT or M-DCOT can ameliorate POI-associated GI motility disorder,probably through downregulation of inflammatory responses along passway,and M-DCQT plays a more significant role in controlling serum inflammatory cytokine levels in POI mice.Objective:To investigate the effect and mechanism of modified Da-Cheng-Qi-Tang(M-DCQT)on gastrointestinal motility in mice with postoperative ileus(POI),on the basis of the results from the first part of the study.Methods:48 adult C57BL/6 mice were were randomly divided into control group(n =6),sham operation group(n =6),POI group(n=6)and M-DCQT group(n=6).POI model was induced by standardized small intestinal interference.Postoperative gavage was given to drinking water(control,sham,POI group)or M-DCQT group twice a day.Gastrointestinal motional function,intestinal tissue morphology,local neurotransmitters,serum levels of gastrointestinal peptides were observed at 24 and48 hours after surgery.The structure and diversity of intestinal mucosal flora were detected by 16 S high-throughput sequencing,and serum pro-inflammatory cytokines were detected by high-throughput liquid microarray.Results:Compared with the control group or sham operation group,POI mice showed a reduction of gastrointestinal expulsion,congestion and edema in intestinal mucosa,and changes in intestinal bacterial structure and diversity,which were alleviated to different extent after M-DCQT treatment.Serum levels of pro-inflammatory cytokines,such as IL-1,IL-6,and TNF-αwere significantly higher in the POI group at24 h and 48 h after surgery than that in the control group or in the sham group(p<0.05 or p<0.01),but MCP-1 and IL-17 increased significantly in the POI group at24h(p<0.05).At the same time,POI mice had increased serum level of vasoactive intestinal peptide,decreased serum level of motilin,and decreased serotonin and increased histamine levels in ileum and colon tissues,which were significantly different from those in the control group or in the sham operation group(p<0.05 or p<0.01).These anomalies were also reversed after M-DCQT treatment(p<0.05 or p<0.01).Conclusion:M-DCQT could effectively improve the gastrointestinal motility,and the mechanism may be related to its reduction ofthe inflammatory response,the changes of intestinal mucosal bacteria and the imbalance of gastrointestinal peptides in POI mice.