The Roles of Tight Junctions and Claudin-1 in the Microbubble-Mediated Ultrasound-Induced Enhancement of Drug Concentrations in Rat Prostate.

Although microbubble-mediated ultrasound irradiation can enhance the prostate permeability, little is known about the mechanism. In our study, the healthy, adult male SD rats were divided into four groups: the BC, US, MB, and MMUS groups. 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 TJs were observed by light and transmission electron microscopy. Western blot was used to assess claudin-1 expression. After treatment of microbubble-mediated ultrasound irradiation, the cefuroxime concentrations in the prostate were significantly increased. HE staining demonstrated that the gland epithelial cell layer became dropsical, thick, and disordered. In transmission electron microscopy, the TJs 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 prostates exposed to microbubble or ultrasound alone, as well as the healthy control rats. In conclusion, microbubble-mediated ultrasound irradiation significantly enhanced the prostate permeability and improve the cefuroxime concentrations in prostate. The changes in TJs structure and the decreased claudin-1 expression may play important roles in this process.