Study On The Mechanism Of Porous Se@SiO₂ Nanosphere Coated Catheter Promoting Wound Recovery After Transurethral Resection Of The Prostate

Objective:To produce porous Se@SiO₂ nanosphere-coated catheter and explore their effect on the wound healing of prostate urethra after transurethral resection of prostate?TURP?as well as the molecular mechanism,which may provide an alternative option for reducing postoperative complications of prostate.Methods:1.Porous Se@SiO₂ nanospheres were synthesized,and the structure was identified by XRD and TEM.The reactive oxygen species?ROS?scavenging ability and biosafety were determined by DCFH-DA staining.In order to produce the coated catheter,porous Se@SiO₂ nanospheres were dissolved in chitosan solution.Then coating thickness,Se release rate and coating stability of the catheter were also detected.2.The TURP model of beagle dogs was constructed and they were randomly divided into Se@SiO₂ group and control group.The wound healing speed and proliferation,migration and differentiation of prostatic basal cells were compared by H&E staining.The residual concentration of Se in tissues,blood and urine was measured by ICP-AES.The liver and kidney functions and the activity of antioxidant enzymes of beagle dogs were determined by biochemical analysis.3.The macrophage polarization in prostatic urethra wound tissue was detected by immunofluorescence staining.The effect of porous Se@SiO₂ nanospheres on the polarization of macrophages and NF-?B pathway were determined using flow cytometry and Western blot in vitro.Results:1.Porous Se@SiO₂ nanosphere-coated catheters were successfully produced.The nanocomposites had outstanding biosafety and could improve the antioxidative activity of macrophages.The release rate of Se was not affected by the coating thickness,and the coating was stable within 1 minute after catheter was indwelled.2.The TURP model of beagle dogs was constructed.Compared with the control group,the recovery speed of the wound was remarkably accelerated in Se@SiO₂ group,and proliferation,migration and differentiation of basal cells were promoted.The levels antioxidant enzymes in the wound tissue of Se@SiO₂ group were higher than those in the control group.The Se concentration was only increased in the wound tissue,and there was no obvious liver and kidney dysfunction or major organ damage in Se@SiO₂ group.3,Porous Se@SiO₂ nanosphere-coated catheter can reduce the number of M1macrophages in the prostatic urethra wound tissue,and up-regulate the number of M2macrophages.The levels of genes and cytokines of M1/M2 macrophages were also decreased/increased,respectively.Porous Se@SiO₂ nanospheres significantly reduced the activation of NF-?B pathway which was stimulated by H₂O₂ in macrophages,thereby shifting macrophage polarization toward M2 phenotype in vitro.Conclusions:Porous Se@SiO₂ nanospheres shift the polarization of macrophages to M2 phenotype by inhibiting the ROS-NF-?B pathway.Indwelling porous Se@SiO2nanosphere-coated catheter could promote re-epithelialization of the prostatic urethra wound while ensuring biocompatibility.It might be an effective method to improve wound recovery after the resection of the prostate.