Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan.
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan City 333323, Taiwan.
Int J Mol Sci. 2020 May 31;21(11):3953. doi: 10.3390/ijms21113953.
Non-bacterial prostatitis is an inflammatory disease that is difficult to treat. Oligonucleotide aptamers are well known for their stability and flexibility in conjugating various inflammatory molecules. In this study, we investigated the effects of inflammatory cytokine-targeting aptamers (ICTA), putative neutralizers of TNF-alpha and IL-1 beta activation, on local carrageenan-induced prostate inflammation, allodynia, and hyperalgesia in rats. In vitro evaluation confirmed the binding capability of ICTA. Intraprostatic injection of carrageenan or control vehicle was performed in six-week-old rats, and ICTA (150 µg) or vehicle was administered in the prostate along with carrageenan injection. The von Frey filament test was performed to determine mechanical allodynia, and prostate inflammation was examined seven days after drug administration. Local carrageenan administration resulted in a reduction of the tactile threshold. The levels of mononuclear cell infiltration, pro-inflammatory cytokine interleukin-1 beta (b), caspase-1 (casp-1), and Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing proteins 1 and 3 (NALP1 and NALP3) in the prostate of rats were increased seven days after carrageenan injection. Treatment with ICTA significantly attenuated the carrageenan-induced hyperalgesia and reduced the elevated levels of proteins including TNF-a and IL-1b in the rats. Apoptosis markers, B-cell lymphoma 2-associated X protein (Bax) and caspase-3, were elevated in ICTA-treated Chronic pelvic pain syndrome (CPPS) rats. These results suggest that ICTA provides protection against local carrageenan-induced enhanced pain sensitivity, and that the neutralization of proinflammatory cytokines may result in inflammatory cell apoptosis.
非细菌性前列腺炎是一种难以治疗的炎症性疾病。寡核苷酸适体以其在连接各种炎症分子方面的稳定性和灵活性而闻名。在这项研究中，我们研究了炎症细胞因子靶向适体（ICTA），即 TNF-α和 IL-1β激活的假定中和剂，对大鼠局部角叉菜胶诱导的前列腺炎症、痛觉过敏和痛觉过敏的影响。体外评估证实了 ICTA 的结合能力。在六周龄大鼠中进行前列腺内注射角叉菜胶或对照载体，然后在前列腺内注射角叉菜胶的同时给予 ICTA（150μg）或载体。使用 Von Frey 细丝试验测定机械性痛觉过敏，并且在给药后七天检查前列腺炎症。局部角叉菜胶给药导致触觉阈值降低。单核细胞浸润、促炎细胞因子白细胞介素-1β（b）、半胱天冬酶-1（casp-1）和核苷酸结合寡聚结构域、亮氨酸丰富重复和吡喃结构域包含蛋白 1 和 3（NALP1 和 NALP3）的水平在角叉菜胶注射后七天在大鼠前列腺中增加。ICTA 治疗显著减弱了角叉菜胶诱导的痛觉过敏，并降低了大鼠中升高的 TNF-a 和 IL-1b 等蛋白水平。凋亡标志物 B 细胞淋巴瘤 2 相关 X 蛋白（Bax）和半胱天冬酶-3 在 ICTA 治疗的慢性盆腔疼痛综合征（CPPS）大鼠中升高。这些结果表明，ICTA 提供了对局部角叉菜胶诱导的增强疼痛敏感性的保护作用，并且中和促炎细胞因子可能导致炎症细胞凋亡。
