Prostate-derived IL-1β upregulates expression of NMDA receptor in the paraventricular nucleus and shortens ejaculation latency in rats with experimental autoimmune prostatitis.
Prostate-derived IL-1β upregulates expression of NMDA receptor in the paraventricular nucleus and shortens ejaculation latency in rats with experimental autoimmune prostatitis.
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DOI：
10.4103/aja202142
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发表时间：
2022-03
影响因子：
2.9
通讯作者：
Xia JD
中科院分区：
文献类型：
--
作者：
Yang J;Luan JC;Chen JH;Zhang QJ;Xue JX;Wang YM;Zhu GQ;Song NH;Wang ZJ;Xia JD
实验性自身免疫性前列腺炎（EAP）诱导的持续性炎症免疫反应可显著上调室旁核（PVN） n -甲基- d -天冬氨酸（NMDA）受体的表达。然而，其机制尚未阐明。在此，我们通过比较EAP大鼠与对照组外周血和脑脊液（CSF）中的炎症细胞因子水平，筛选出目标前列腺源性炎症细胞因子（PDICs）。在确定目标PDIC后，通过初始交配行为测试（CBT）的合格雄性在双侧PVN上植入导管。然后，将患者随机分为4个亚组（EAP-1、EAP-2、Control-1、Control-2）。恢复1周后，EAP-1大鼠微注射目标PDIC抑制剂，Control-1大鼠微注射目标PDIC，而EAP-2和Control-2亚组仅注射等量的人工脑脊液（aCSF）。结果显示，与对照组相比，EAP大鼠前列腺中只有白细胞介素-1β (IL-1β) mrna表达显著升高（P < 0.001）， EAP组血清和脑脊液中mrna表达均显著升高（P = 0.001）。因此，IL-1β被确定为通过血脑屏障影响中枢神经系统的靶点PDIC。此外，在最后三个cbt中，EAP-1亚组表现出逐渐延长的射精潜伏期（EL）（均P < 0.01），并且在中央给药10天后，与各自的对照组相比，PVN中NMDA NR1亚基的表达显著降低（P = 0.043）。然而，对照组-1亚组在同步给予IL-1β后，EL逐渐缩短（P < 0.01）， NR1表达显著升高（P = 0.004）。因此，我们确定IL-1β是缩短EAP大鼠EL的主要PDIC。然而，IL-1β上调NMDA表达的具体分子机制有待进一步研究。
Experimental autoimmune prostatitis (EAP)-induced persistent inflammatory immune response can significantly upregulate the expression of N-methyl-D-aspartic acid (NMDA) receptors in the paraventricular nucleus (PVN). However, the mechanism has not yet been elucidated. Herein, we screened out the target prostate-derived inflammation cytokines (PDICs) by comparing the inflammatory cytokine levels in peripheral blood and cerebrospinal fluid (CSF) between EAP rats and their controls. After identifying the target PDIC, qualified males in initial copulatory behavior testing (CBT) were subjected to implanting tubes onto bilateral PVN. Next, they were randomly divided into four subgroups (EAP-1, EAP-2, Control-1, and Control-2). After 1-week recovery, EAP-1 rats were microinjected with the target PDIC inhibitor, Control-1 rats were microinjected with the target PDIC, while the EAP-2 and Control-2 subgroups were only treated with the same amount of artificial CSF (aCSF). Results showed that only interleukin-1β (IL-1β) had significantly increased mRNA-expression in the prostate of EAP rats compared to the controls (P < 0.001) and significantly higher protein concentrations in both the serum (P = 0.001) and CSF (P < 0.001) of the EAP groups compared to the Control groups. Therefore, IL-1β was identified as the target PDIC which crosses the blood-brain barrier, thereby influencing the central nervous system. Moreover, the EAP-1 subgroup displayed a gradually prolonged ejaculation latency (EL) in the last three CBTs (all P < 0.01) and a significantly lower expression of NMDA NR1 subunit in the PVN (P = 0.043) compared to the respective control groups after a 10-day central administration of IL-1β inhibitors. However, the Control-1 subgroup showed a gradually shortened EL (P < 0.01) and a significantly higher NR1 expression (P = 0.004) after homochronous IL-1β administration. Therefore, we identified IL-1β as the primary PDIC which shortens EL in EAP rats. However, further studies should be conducted to elucidate the specific molecular mechanisms through which IL-1β upregulates NMDA expression.