Deng Shou-Long, Zhang Bao-Lu, Reiter Russel J, Liu Yi-Xun
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
Marine Consulting Center of Natural Resources of the People's Republic of China, Beijing 100071, China.
Antioxidants (Basel). 2020 Dec 14;9(12):1277. doi: 10.3390/antiox9121277.
Gram-negative bacterial infections of the testis can lead to infectious orchitis, which negatively influences steroid hormone synthesis and spermatogenesis. Lipopolysaccharide (LPS), a major component of the Gram-negative bacterial cell wall, acts via toll like receptors 4 (TLR4) to trigger innate immune responses and activate nuclear factor kappa B signaling. The protective mechanisms of melatonin on LPS-induced infectious orchitis have not been reported. Herein, we developed an LPS-induced sheep infectious orchitis model. In this model, the phagocytic activity of testicular macrophages (TM) was enhanced after melatonin treatment. Moreover, we found that melatonin suppressed secretion of TM pro-inflammatory factors by suppressing the p38MAPK pathway and promoting Leydig cell testosterone secretion. Expressions of GTP cyclohydrolase-I and NADPH oxidase-2 were reduced by melatonin while heme oxygenase-1 expression was up-regulated. Thus, melatonin reduced the severity of LPS-induced orchitis by stimulating antioxidant activity. The results of this study provide a reference for the treatment of acute infectious orchitis.
革兰氏阴性菌感染睾丸可导致感染性睾丸炎，这会对类固醇激素合成和精子发生产生负面影响。脂多糖（LPS）是革兰氏阴性菌细胞壁的主要成分，通过Toll样受体4（TLR4）发挥作用，触发先天免疫反应并激活核因子κB信号通路。褪黑素对LPS诱导的感染性睾丸炎的保护机制尚未见报道。在此，我们建立了LPS诱导的绵羊感染性睾丸炎模型。在该模型中，褪黑素处理后睾丸巨噬细胞（TM）的吞噬活性增强。此外，我们发现褪黑素通过抑制p38丝裂原活化蛋白激酶（p38MAPK）途径和促进睾丸间质细胞睾酮分泌，抑制了TM促炎因子的分泌。褪黑素降低了鸟苷三磷酸环化水解酶-I（GTP cyclohydrolase-I）和烟酰胺腺嘌呤二核苷酸磷酸氧化酶-2（NADPH oxidase-2）的表达，同时上调了血红素加氧酶-1（heme oxygenase-1）的表达。因此，褪黑素通过刺激抗氧化活性降低了LPS诱导的睾丸炎的严重程度。本研究结果为急性感染性睾丸炎的治疗提供了参考。
