Low-Intensity Extracorporeal Shock Wave Therapy For The Treatment Of CP/CPPS

Background:Chronic prostatitis/chronic pelvic pain syndrome（CP/CPPS）is a common disease in urology with a high incidence in the population,the global prevalence of CP/CPPS is approximately 2.2%～16.0%.Although CP/CPPS isn’t life-threatening,the long-term and constant pain can seriously affect the quality of life of patients.At present,there are many treatments for CP/CPPS,but the therapeutic effect is unsatisfactory due to unknown pathogenesis and complex etiology.The development of innovative and effective treatment modalities was needed urgently.Low-energy extracorporeal shock wave therapy（Li-ESWT）has been reported to be effective in the treatment of CP/CPPS,however,the underlying mechanism remains to be investigated.Objective:To further understand the pathogenesis and pathological features of CP/CPPS,and to interrogated the efficacy and the mechanism of Li-ESWT in the treatment of CP/CPPS.Methods:In this study,the models were established based on the pathological characteristics of CP/CPPS autoimmune inflammation,which was applied to RWPE-1cells and EAP rats by Li-ESWT in vivo and in vitro.1.LPS was employed to induce inflammation in RWPE-1 cells to establish in vitro model.Cells were randomly divided into three groups:control group,LPS（lipopolysaccharide）group,or Li-ESWT group（LPS-induced RWPE-1 managed by Li-ESWT）.After the Li-ESWT treatment,the levels of inflammatory factors and oxidative stress were assayed by q RT-PCR,redox assay kits and ROS fluorescent probe.2.Animal models were established by chemical stimulation method and treated with li-ESWT for different energy density.The appropriate Li-ESWT energy density was determined by Von Frey Filament pain measurement method.We then established a rat model of experimental autoimmune prostatitis（EAP）by injecting prostatic protein homogenate mixed with complete Freund’s adjuvant.According to the corresponding management methods SD rats were divided into Control group,EAP group and EAP+Li-ESWT group.Von Frey Filament was used to quantify pelvic hyperalgesia in the rats.Prostates tissues from each group were collected for IHC,oxidation stress,and Western blot analysis.Results:1.The expression of TNF-α,IL-1βand IL-6 genes and oxidative stress levels in LPS group were significantly higher than those in Control group.After treatment of RWPE-1 cells with Li-ESWT at an energy density of 0.09 m J/mm~2,TNF-α,IL-1β,and IL-6 gene expression was significantly decreased compared with the LPS group,and anti-oxidation was enhanced,which in turn improved the intracellular oxidative stress state.2.Chemical stimulation-induced animal models were used to determine the appropriate energy density of 0.20 m J/mm~2 by Von Frey Filament algometry for rats.Von Frey Filament pain data was used to represent pain sensitivity in the pelvic region of the animal model,which was always at baseline in the control group and significantly improved in the EAP+Li-ESWT group compared with the EAP group.Pathological sections of the prostate showed that Li-ESWT was able to significantly improve inflammatory cell infiltration,interstitial edema,congestion,fibrosis,and destruction of glandular epithelial cells in the prostate of EAP rats.IHC showed that the expression of cytokines TNF-α,IL-1β,IL-6,COX-2 and SP in prostate was significantly reduced in the Li-ESWT group compared with the EAP group.In addition,Li-ESWT decreased the level of oxidative stress in the prostate of EAP rats and improved the antioxidant capacity of the tissue.Western blot suggested that Li-ESWT inhibited AKT and FOXO1 phosphorylation in the prostate tissue of EAP rats,followed by up-regulation of CAT protein expression.Conclusion:The Pathogenesis of CP/CPPS has a close relationship with autoimmune inflammation.During the course of the disease,the local microenvironment of the prostate is disturbed by the combined action of immune dysregulation,oxidative stress and pain factor release.The significant effect of Li-ESWT,possibly by inhibiting the phosphorylation of PI3K/AKT/FOXO1 signaling pathway,enhances anti-inflammatory,antioxidant and pain suppression in autoimmune prostatitis.It implies that Li-ESWT can present a potential therapeutic option for the treatment of CP/CPPS.