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 advant...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-PLGA 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 solution group(intestinal anastomosis+intraperitoneal injection of Dex), and Dex microsphere 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 significantly activated the PI3K/Akt pathway, reduced inflammatory cytokine levels, and improved the histological healing status and mechanical strength of the anastomosis(P<0.001). While the core pharmacological effects were comparable between the Dex microsphere 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 incidence 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 effectively improves intestinal anastomotic healing in rats by activating the PI3K/Akt pathway and inhibiting inflammatory response, demonstrating clear clinical value. Dex-PLGA sustained-release microspheres offer distinct advantages in postoperative recovery quality and complication control, providing a new direction for optimizing clinical administration methods for Dex in regulating intestinal anastomotic healing.展开更多
基金Class Ⅱ Project of Longyan Science and Technology Bureaugrant number:2022LYF17099
文摘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-PLGA 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 solution group(intestinal anastomosis+intraperitoneal injection of Dex), and Dex microsphere 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 significantly activated the PI3K/Akt pathway, reduced inflammatory cytokine levels, and improved the histological healing status and mechanical strength of the anastomosis(P<0.001). While the core pharmacological effects were comparable between the Dex microsphere 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 incidence 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 effectively improves intestinal anastomotic healing in rats by activating the PI3K/Akt pathway and inhibiting inflammatory response, demonstrating clear clinical value. Dex-PLGA sustained-release microspheres offer distinct advantages in postoperative recovery quality and complication control, providing a new direction for optimizing clinical administration methods for Dex in regulating intestinal anastomotic healing.
