摘要Objective:To investigate the mechanism by which dexmedetomidine(Dex)regulates inflammatory response and improves intestinal anastomotic healing via the PI3K/Akt signaling pathway,and to evaluate the delivery advantages of Dex-PL-GA sustained-release microspheres,providing experimental evidence for optimizing clinical Dex administration.Methods:Sixty SPF-grade male sprague-dawley(SD)rats were randomly divided into 3 groups(n=20):Sham group(only laparotomy),Dex solu-tion group(intestinal anastomosis+intraperitoneal injection of Dex),and Dex micro-sphere group(intestinal anastomosis+local implantation of Dex-PLGA microspheres).Dex-PLGA microspheres were prepared and characterized by emulsification-solvent evaporation method.Anastomotic tensile strength was measured at 3,7,and 14 days post-operation.Protein expression of the PI3K/Akt pathway,serum levels of IL-6 and TNF-α,and histological scores were evaluated on postoperative 7th day.Postoperative recovery indicators and complication rates were also recorded.Results:Dex signifi-cantly activated the PI3K/Akt pathway,reduced inflammatory cytokine levels,and im-proved the histological healing status and mechanical strength of the anastomosis(P<0.001).While the core pharmacological effects were comparable between the Dex mi-crosphere and solution groups,the microsphere group demonstrated higher food intake at 24 h and better weight recovery rates at 7 days post-operation.Notably,the inci-dence of anastomotic leakage in the microsphere group was reduced to 0(P<0.05).The Dex-PLGA microspheres exhibited regular morphology,an average particle size of(235.62±18.50)nm,an encapsulation efficiency of 82.3%,and a cumulative release rate of 92%over 14 days,achieving sustained drug release.Conclusion:Dex effec-tively improves intestinal anastomotic healing in rats by activating the PI3K/Akt path-way and inhibiting inflammatory response,demonstrating clear clinical value.Dex-PLGA sustained-release microspheres offer distinct advantages in postoperative re-covery quality and complication control,providing a new direction for optimizing clin-ical administration methods for Dex in regulating intestinal anastomotic healing.