The Effect And Mechanism Of Microbubble-mediated Ultrasound On Enhancement Of Drug Permeability In Prostate Tissue

Background: The incidence of chronic prostatitis(CP)is high,but the treatment is difficult and it repeated attacks,the main reason is the existence of "blood-prostate barrier" and its selective permeability of material between prostate and blood.Studies have shown that microbubble-mediated ultrasound can significantly improve the prostate tissue permeability,this technology may become a new method for the treatment of CP,but whether this method can promote the drug into the prostate tissue and its possible mechanism are not clear,therefore,we further clarify the effect and mechanism of microbubble-mediated ultrasound on enhancement of drug permeability in prostate tissue,this may provide experimental evidence for the clinical treatment of CP.Part 1 The effect of microbubble-mediated ultrasound on enhancement of drug permeability in prostate tissueObjective: To observe the effect of microbubble-mediated ultrasound on the concentrations of drug in rat prostate tissue.Methods: Male Sprague-Dawley rats were classified into experimental group and control group,randomly.Rats were given cefuroxime and microbubble via the tail vein in the experimental group,and then the prostates were exposed to ultrasonic irradiation for five minutes;the control group was given cefuroxime and the same amount of normal salin via the tail vein,and then given sham ultrasonic irradiation for five minutes.After ultrasound irradiation,the prostate was taken and became homogenate,cefuroxime concentration in prostate tissue was measured by high performance liquid chromatograph(HPLC).Results: Compared to the control group,the concentration of cefuroxime was significant higher in the experimental group,and the difference was statistically significant,P<0.05.Conclusion: Microbubble-mediated ultrasound can significantly improve the permeability of prostate tissue.Part 2 The mechanism of microbubble-mediated ultrasound on enhancement of permeability of prostate tissueObjective: To study the mechanism of microbubble-mediated ultrasound on enhancement of permeability of prostate tissue.Methods: Healthy,adult male Sprague-Dawley rats were classified into blank control group(BC group),ultrasound group(US group),MB group(MB group),and MB-mediated ultrasound group(MMUS group).A therapeutic ultrasound apparatus was used to treat the rats prostates in the presence of circulating MBs.Cefuroxime was injected to assess prostate permeability by HPLC.The structures of prostate tissues and tight junctions were observed by light and transmission electron microscopy.Western blot was used to assess claudin-1 expression.Results: After treatment of microbubble-mediated ultrasound irradiation,permeability of prostate tissue was significantly increased.HE staining demonstrated that the gland epithelial cell layer became dropsical,thick,and disordered.In transmission electron microscopy,the tight junctions between adjacent capillary endothelial cells or gland epithelial cells were disjointed and partly interrupted.Furthermore,western blot showed the expression of claudin-1 was significantly decreased.However,these findings were not observed in the other three groups.Conclusion: Microbubble-mediated ultrasound irradiation significantly enhanced the prostate permeability.Tight junctions between capillary endothelial cells and epithelial cells of the prostate gland and the protein claudin-1 may play important roles in the process.