| Part Ⅰ Study on Effect and Mechanism of Alcohol on Chronic Non-bacterial ProstatitisBackground Chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)is a prevalent disease of the urogenital system.Alcohol has been reported to be closely related to CP/CPPS.Thus,we intended to verify the role of alcohol in CP/CPPS and determine the underlying mechanism.Methods We induced experimental autoimmune prostatitis(EAP)mouse model by intradermally injecting a mixture of prostate antigens(PAgs)and complete Freund’s adjuvant on days 0 and 28.Mice were treated with alcohol(control-alcohol and EAP-alcohol groups)or vehicle(control-vehicle,and EAP-vehicle groups)from day 32 to 42.Forty-two days after PAg injection,the pathological appearance of the prostate tissues was evaluated,and histological analyses of the prostate were performed.Chronic pelvic pain was assessed by applying von Frey filaments to the lower abdomen.Pro-inflammatory cytokines were detected by enzyme-linked immunosorbent assay tests.Then,we explored the effects of the NLRP3 inhibitor MCC950 on chronic pelvic pain and prostatic inflammation in this model.Results Histological analyses showed diffuse inflammation in the stromal tissues that were characterized by severe infiltration of neutrophils and mononuclear cells in mice in the EAP-alcohol group compared with EAP-vehicle group.Chronic pain tests showed that the response frequency was significantly increased using a von Frey filament at forces of 0.4,1.0,and 4.0?g in EAP-alcohol group compared with EAP-vehicle(P?<0.05).The levels of pro-inflammatory cytokines,including interferon(IFN)-γ,tumor necrosis factor(TNF)-α,IL-17,and IL-1β were all significantly elevated in EAP-alcohol group compared with the EAP-vehicle group(P?<?0.05).However,between the control-alcohol and control-vehicle groups,chronic pain tests,histological assays,and cytokine determinations showed no differences.Furthermore,our results demonstrated that MCC950 could decrease the expression level of NLRP3 inflammasome-related proteins including NLRP3,ASC,and caspase-1.The chronic pain tests,histological assays,and cytokine determinations showed that MCC950 could attenuate the chronic pain and prostatic inflammation through the inhibition of the NLRP3 inflammasome.Conclusions This study indicated that alcohol could aggravate the severity of prostatic inflammation in EAP model though activating the NLRP3 inflammasome.Furthermore,the role of MCC950 in inhibiting NLRP3 inflammasome and decreasing IL‐1β secretion alleviate EAP severity may show that it is a promising therapeutic agent for CP/CPPS.Part Ⅱ Study on the Therapeutic Effect and Mechanism of Eriocalyxin B on Chronic Non-bacterial ProstatitisBackground Chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)is a very common disease in males.Eriocalyxin B(Eri B)is a natural diterpenoid possessing strong anti-inflammatory activity.However,the effects of Eri B on CP/CPPS had not been studied.Thus,we intended to study the role of Eri B on CP/CPPS with an experimental autoimmune prostatitis(EAP)model.Methods EAP mice received intraperitoneal injection of Eri B 5.0 mg/kg/d and 10.0 mg/kg/d(EAP+Eri B5.0 group,EAP+Eri B10.0 group).Then,histothological appearances of the prostate tissue were evaluated.Chronic pelvic pain was tested by using von Frey filaments to the lower abdominal area.Inflammatory cytokines were measured by ELISA tests.Results In results,compared to mice in EAP group,the chronic pain development,histological appearances and cytokines levels demonstrated that Eri B could alleviate the severity of EAP in a dose-dependent manner.The mechanism research found that the up-regulating PI3K/Akt/ m TOR and autophagy signal pathways and down-regulated NF-κB pathway may be the potential mechanisms.Conclusions In summary,the present study suggested that Eri B could alleviate the severity of CP/CPPS in an EAP mouse model.These findings broaden the value of Eri B as a promising candidate for the treatment of CP/CPPS. |
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