Department of Urology and Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Shenzhen Key Lab of Drug Addiction, The Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen-HongKong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China.
Front Immunol. 2020 Sep 9;11:574212. doi: 10.3389/fimmu.2020.574212. eCollection 2020.
Experimental autoimmune prostatitis (EAP) is a well-established model induced by an autoimmune response to prostate antigen. The symptomatic, pathological, and immunological characteristics of EAP animals are highly consistent with human chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), which makes EAP an ideal model for this disease. Here, we investigate the influence of EAP on male rat sexual function and the efficacy of anti-inflammatory therapy with celecoxib. EAP rat models were established using male Wistar rats. Rats were randomly assigned to a normal control group, an EAP model group, or an EAP model with celecoxib treatment group (celecoxib group). Behavioral changes, sexual behavioral changes, and erectile function were estimated using an open-field test, a sucrose consumption test, mating experiments, and by intracavernous pressure/mean arterial pressure ratio (ICP/MAP). Histological changes in the prostate were observed by HE staining, and the serum inflammatory factors IL-1β and TNF-α levels were measured by enzyme-linked immunosorbent assay. In addition, serotonin (5-hydroxytryptamine, 5-HT), 5-HT receptor, 5-HT receptor, and serotonin transporter (SERT) expression levels in the hippocampus and spinal cord (T13-L1, L5-S2) were examined by immunohistochemistry and western blot analysis. Results showed that EAP rats exhibited characteristics of depression, decreased sexual drive, premature ejaculation, and increased threshold of penile erection. Moreover, all these changes were effectively alleviated by celecoxib. Significant increases in prostatic interstitial infiltration by inflammatory cells and in serum IL-1β and TNF-α levels were observed in EAP rats, and these were partially reduced by celecoxib. Additionally, the expression pattern of serotonin system regulators in the hippocampus and spinal cord were altered in EAP model rats, including a decrease in 5-HT levels and an increase in 5-HT receptor levels. In conclusion, autoimmune prostatitis impaired rat sexual function, and this was effectively prevented by anti-inflammatory therapy with celecoxib. Moreover, a serotonin system disorder in the central nervous system was likely mediated via inflammation in EAP rats.
实验性自身免疫性前列腺炎（EAP）是一种通过针对前列腺抗原的自身免疫反应诱导的成熟模型。EAP 动物的症状、病理和免疫学特征与人类慢性前列腺炎/慢性骨盆疼痛综合征（CP/CPPS）高度一致，这使得 EAP 成为该疾病的理想模型。在这里，我们研究了 EAP 对雄性大鼠性功能的影响以及塞来昔布抗炎治疗的疗效。使用雄性 Wistar 大鼠建立 EAP 大鼠模型。大鼠随机分为正常对照组、EAP 模型组和 EAP 模型加塞来昔布治疗组（塞来昔布组）。通过旷场试验、蔗糖消耗试验、交配实验和海绵体内压/平均动脉压比（ICP/MAP）评估行为变化、性行为变化和勃起功能。通过 HE 染色观察前列腺的组织学变化，通过酶联免疫吸附试验测量血清炎症因子 IL-1β 和 TNF-α 水平。此外，通过免疫组织化学和 Western blot 分析检测海马和脊髓（T13-L1、L5-S2）中 5-羟色胺（5-HT）、5-HT 受体、5-HT2A 受体和 5-HT 转运体（SERT）的表达水平。结果表明，EAP 大鼠表现出抑郁特征、性欲下降、早泄和阴茎勃起阈值增加。此外，塞来昔布可有效缓解所有这些变化。EAP 大鼠前列腺间质炎症细胞浸润和血清 IL-1β 和 TNF-α 水平显著增加，塞来昔布可部分减轻。此外，EAP 模型大鼠海马和脊髓中 5-羟色胺系统调节剂的表达模式发生改变，包括 5-HT 水平降低和 5-HT 受体水平升高。总之，自身免疫性前列腺炎损害了大鼠的性功能，而塞来昔布的抗炎治疗可有效预防。此外，EAP 大鼠中枢神经系统中 5-羟色胺系统紊乱可能是通过炎症介导的。
