Intermedin attenuates LPS-induced inflammation in the rat testis.
Intermedin attenuates LPS-induced inflammation in the rat testis.
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DOI：
10.1371/journal.pone.0065278
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhang JV
中科院分区：
文献类型：
--
作者：
Li L;Ma P;Liu Y;Huang C;O WS;Tang F;Zhang JV
最早被报道为心血管系统中的血管活性肽，中间肽（IMD），也称为肾上腺髓质素2（ADM 2），是一种具有多种有效作用的激素，包括其对肺、中枢神经、心血管和肾系统的抗氧化作用。虽然IMD可能在滋养层细胞侵入、早期胚胎发育和卵丘细胞-卵母细胞相互作用中发挥一定作用，但IMD在男性生殖系统中的作用还有待研究。本文报道了我们的研究结果，IMD的基因表达，其受体成分和蛋白定位在睾丸。在大鼠模型中，细菌脂多糖（LPS）诱导非典型睾丸炎，并且LPS处理上调IMD及其受体组分蛋白之一，即受体活性修饰蛋白2（RAMP 2）的表达。IMD降低了血浆和睾丸活性氧（ROS）的产生水平，减弱了促炎细胞因子肿瘤坏死因子α（TNFα）、白细胞介素6（IL 6）和白细胞介素1 β（IL 1 β）基因表达的增加，挽救了精子发生，并防止了LPS引起的血浆睾酮水平的降低。在过氧化氢处理的大鼠原代Leydig细胞培养中也观察到IMD对类固醇合成的恢复作用。我们的研究结果表明，IMD在精子发生和类固醇生成中起着重要的保护作用，这表明IMD在睾丸炎等病理条件下具有治疗潜力。
First reported as a vasoactive peptide in the cardiovascular system, intermedin (IMD), also known as adrenomedullin 2 (ADM2), is a hormone with multiple potent roles, including its antioxidant action on the pulmonary, central nervous, cardiovascular and renal systems. Though IMD may play certain roles in trophoblast cell invasion, early embryonic development and cumulus cell-oocyte interaction, the role of IMD in the male reproductive system has yet to be investigated. This paper reports our findings on the gene expression of IMD, its receptor components and its protein localization in the testes. In a rat model, bacterial lippolysaccharide (LPS) induced atypical orchitis, and LPS treatment upregulated the expression of IMD and one of its receptor component proteins, i.e. receptor activity modifying protein 2 (RAMP2). IMD decreased both plasma and testicular levels of reactive oxygen species (ROS) production, attenuated the increase in the gene expression of the proinflammatory cytokines tumor necrosis factor alpha (TNFα), interleukin 6 (IL6) and interleukin 1 beta (IL1β), rescued spermatogenesis, and prevented the decrease in plasma testosterone levels caused by LPS. The restorative effect of IMD on steroidogenesis was also observed in hydrogen peroxide-treated rat primary Leydig cells culture. Our results indicate IMD plays an important protective role in spermatogenesis and steroidogenesis, suggesting therapeutic potential for IMD in pathological conditions such as orchitis.
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