Melatonin attenuates prostatic inflammation and pelvic pain via Sirt1-dependent inhibition of the NLRP3 inflammasome in an EAP mouse model
Melatonin attenuates prostatic inflammation and pelvic pain via Sirt1-dependent inhibition of the NLRP3 inflammasome in an EAP mouse model
复制标题
在 EAP 小鼠模型中，褪黑激素通过 Sirt1 依赖性抑制 NLRP3 炎症小体减轻前列腺炎症和盆腔疼痛
DOI：
10.1002/pros.24214
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发表时间：
2021-08-21
期刊：
影响因子：
2.8
通讯作者：
Liang, Chao-Zhao
中科院分区：
文献类型：
--
作者：
Chen, Jing;Zhang, Li-Gang;Liang, Chao-Zhao
慢性前列腺炎/慢性骨盆疼痛综合征（CP/CPPS）是一种常见的男性泌尿生殖系统疾病。褪黑激素作为一种神经内分泌激素，具有多种生物学功能，其中抗炎作用近年来受到广泛关注。本研究采用实验性自身免疫性前列腺炎（EAP）小鼠模型，探讨褪黑素对CP/CPPS的影响及其机制。方法采用前列腺抗原与完全弗氏佐剂混合液皮下注射的方法建立EAP小鼠模型。第42天，使用苏木精-伊红染色评价前列腺组织的组织学外观。通过耻骨上异常性疼痛评估慢性盆腔疼痛的发展。采用酶联免疫吸附法检测炎症相关细胞因子干扰素-γ、白细胞介素（IL）-17、IL-1 β的水平。然后，采用免疫印迹和免疫组织化学方法，通过检测EAP小鼠CP/CPPS中沉默信息调节因子1（Sirt 1）和NLRP 3炎症相关蛋白的表达，探讨褪黑素的抗炎作用。结果与对照组相比，EAP模型组小鼠盆腔疼痛程度明显加重，弥漫性白细胞浸润严重。在褪黑素治疗组中，前列腺组织的组织学外观、盆腔疼痛发展和促炎细胞因子水平与EAP +二甲基亚砜组相比显著减轻。此外，我们发现褪黑激素的保护作用是通过激活Sirt 1通路和下调NLRP 3炎性体来实现的。结论褪黑素可通过激活Sirt 1抑制NLRP 3炎症体信号通路，减轻EAP小鼠前列腺炎症和盆腔疼痛，为CP/CPPS的治疗提供了一种新的思路。
Background Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male genitourinary system disease. As a neuroendocrine hormone, melatonin possesses a variety of biological functions, among which its anti-inflammatory effects have recently drawn substantial attention. The purpose of the current research was to study the effect of melatonin on CP/CPPS and the underlying mechanisms using a mouse model of experimental autoimmune prostatitis (EAP). Methods The EAP mouse model was successfully established by subcutaneously injecting a mixture of prostate antigen and complete Freund's adjuvant. On Day 42, hematoxylin-eosin staining was used to evaluate the histological appearance of prostate tissues. Chronic pelvic pain development was assessed by suprapubic allodynia. The levels of inflammation-related cytokines, such as interferon-gamma, interleukin (IL)-17, and IL-1 beta, were detected by enzyme-linked immunosorbent assay. Then, we explored the anti-inflammatory effects of melatonin on CP/CPPS by Western blotting and immunohistochemical staining, by measuring the expression of silent information regulator 1 (Sirt1) and NLRP3 inflammasome-related proteins in EAP mice. Results The EAP model mice exhibited severe diffuse leukocyte infiltration and significantly increased pelvic pain compared to the control mice. In the melatonin treatment group, the histological appearance of the prostate tissues, pelvic pain development, and the levels of proinflammatory cytokines were significantly alleviated compared to the EAP + dimethyl sulfoxide group. Furthermore, we found that the protective effects of melatonin were achieved through activation of the Sirt1 pathway and downregulation of the NLRP3 inflammasome. Conclusions The results indicated that melatonin could attenuate prostate inflammation and pelvic pain by inhibiting the NLRP3 inflammasomes signaling pathway through the activation of Sirt1 in mice with EAP, and these efforts should provide a promising therapeutic strategy for CP/CPPS.