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体外冲击波疗法通过抑制 TLR4-NFκB 通路降低前列腺炎大鼠模型中的 COX-2。

Extracorporeal shock wave therapy decreases COX-2 by inhibiting TLR4-NFκB pathway in a prostatitis rat model.

机构信息

Department of Urology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Catholic Integrative Medicine Research Institute, The Catholic University of Korea, Seoul, Republic of Korea.

出版信息

Prostate. 2019 Sep;79(13):1498-1504. doi: 10.1002/pros.23880. Epub 2019 Aug 2.

DOI:10.1002/pros.23880
PMID:31376214
Abstract

BACKGROUND

This study aims to evaluate the effect of extracorporeal shock wave therapy (ESWT) on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and to explore the mechanism.

METHODS

RWPE-2 cells were randomly divided into three groups: (a) RWPE-2 group (normal control), (b) LPS groups (lipopolysaccharide inducing inflammation) and (c) ESWT groups (LPS induced RWPE-2 treated by ESWT). After ESWT was administered, cells and supernatant were collected for enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. In vivo, Sprague-Dawley rats (n = 30) were randomly divided into three groups: (a) normal control group, (b) prostatitis groups, and (c) ESWT groups. Prostatitis rats were induced by 17 β-estradiol and dihydrotestosterone for 4 weeks. After ESWT, prostates of each group were collected for immunohistochemistry, Western blot analysis, and ELISA.

RESULTS

ESWT improved prostatitis by attenuating inflammation (P < .01). ESWT downregulated the expression of cyclooxygenase 2 (COX-2) through inhibiting TLR4-NFκB pathway compared with the LPS group in vitro or prostatitis group in vivo (P < .05). TRAF2 mediates ERK1/2-COX2 pathway. ESWT promotes prostate tissue recovery by stimulating vascular endothelial growth factor expression (P < .01). ESWT could suppress apoptosis in the prostate.

CONCLUSIONS

ESWT improved CP/CPPS and reduced inflammation by degrading COX-2 in microenvironment through TLR4-NFκB-inhibiting pathway. TRAF2 regulator in ERK1/2-COX-2 inhibition significantly reduced inflammation, thus suggesting ESWT may be a potential and promising treatment for CP/CPPS.

摘要

背景

本研究旨在评估体外冲击波疗法(ESWT)对慢性前列腺炎/慢性骨盆疼痛综合征(CP/CPPS)的疗效,并探讨其机制。

方法

RWPE-2 细胞随机分为三组:(a)RWPE-2 组(正常对照组),(b)LPS 组(脂多糖诱导炎症)和(c)ESWT 组(LPS 诱导 RWPE-2 用 ESWT 处理)。ESWT 治疗后,收集细胞和上清液进行酶联免疫吸附测定(ELISA)和 Western blot 分析。体内,将 Sprague-Dawley 大鼠(n=30)随机分为三组:(a)正常对照组,(b)前列腺炎组,和(c)ESWT 组。用 17β-雌二醇和二氢睾酮诱导前列腺炎大鼠 4 周。ESWT 后,收集各组前列腺进行免疫组织化学、Western blot 分析和 ELISA。

结果

ESWT 通过减轻炎症改善前列腺炎(P<0.01)。与 LPS 组或体内前列腺炎组相比,ESWT 通过抑制 TLR4-NFκB 通路下调环氧化酶 2(COX-2)的表达(P<0.05)。TRAF2 介导 ERK1/2-COX2 通路。ESWT 通过刺激血管内皮生长因子表达促进前列腺组织恢复(P<0.01)。ESWT 可抑制前列腺细胞凋亡。

结论

ESWT 通过 TLR4-NFκB 抑制通路降解微环境中的 COX-2 改善 CP/CPPS 并减轻炎症。TRAF2 调节剂抑制 ERK1/2-COX-2 通路显著减轻炎症,提示 ESWT 可能是 CP/CPPS 的一种有潜力和有前途的治疗方法。

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