TNF-α Infusion Impairs Corpora Cavernosa Reactivity
TNF-α Infusion Impairs Corpora Cavernosa Reactivity
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DOI：
10.1111/j.1743-6109.2008.01189.x
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发表时间：
2009-03-01
影响因子：
3.5
通讯作者：
Tostes, Rita C.
中科院分区：
文献类型：
--
作者：
Carneiro, Fernando S.;Zemse, Saiprazad;Tostes, Rita C.
导论.勃起功能障碍（艾德）以及心血管疾病（CVD）与内皮功能障碍和促炎性细胞因子（如肿瘤坏死因子-α（TNF-α））水平升高相关。我们假设TNF-α水平的升高损害了海绵体功能。使用体外器官浴研究来测量用媒介物或TNF-α-（220 ng/kg/min）输注14天的小鼠的海绵体反应性。实时荧光定量聚合酶链反应检测一氧化氮合酶亚型的基因表达。与对照动物相比，TNF-α输注小鼠的海绵体条显示出非肾上腺素能-非胆碱能（NANC）诱导的松弛降低（59.4 +/- 6.2 vs.对照组：76.2 +/- 4.7; 16 Hz）。这些反应与eNOS和nNOS基因表达下降有关（P < 0.05）。在TNF-α输注小鼠的海绵体条中，交感神经介导的以及苯肾上腺素（PE）诱导的收缩反应（PE诱导的收缩; 1.32 +/- 0.06 vs.对照：0.9 +/- 0.09，mN）增加。此外，TNF-α可增加海绵体对内皮素-1和内皮素受体A亚型（ETA）的反应（P < 0.05），并可轻微降低肿瘤坏死因子-α受体1（TNFRI）的表达（P=0.063）。来自TNF-α输注小鼠的海绵体显示出与eNOS和nNOS基因表达降低相关的收缩反应增加和NANC神经介导的舒张减少。这些变化可能触发艾德，并表明TNF-α在勃起功能中起着有害作用。TNF-α作用的阻断可能代表艾德的替代治疗方法，特别是在与该细胞因子水平增加相关的病理条件下。1996年，J.J. FS，Zemse S，Giachini FRC，J.J. ZN，Lima W，Clinton Webb R和Tostes RC。TNF-α输注损害海绵体反应性。J Sex Med 2009;6（suppl 3）：311-319.
Introduction. Erectile dysfunction (ED), as well as cardiovascular diseases (CVDs), is associated with endothelial dysfunction and increased levels of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha).Aim. We hypothesized that increased TNF-alpha levels impair cavernosal function.Methods. In vitro organ bath studies were used to measure cavernosal reactivity in mice infused with vehicle or TNF-alpha-(220 ng/kg/min) for 14 days. Gene expression of nitric oxide synthase isoforms was evaluated by real-time polymerase chain reaction.Results. Cavernosal strips from the TNF-alpha-infused mice displayed decreased nonadrenergic-noncholinergic (NANC)-induced relaxation (59.4 +/- 6.2 vs. control: 76.2 +/- 4.7; 16 Hz) compared with the control animals. These responses were associated with decreased gene expression of eNOS and nNOS (P < 0.05). Sympathetic-mediated, as well as phenylephrine (PE)-induced, contractile responses (PE-induced contraction; 1.32 +/- 0.06 vs. control: 0.9 +/- 0.09, mN) were increased in cavernosal strips from TNF-alpha-infused mice. Additionally, infusion of TNF-alpha increased cavernosal responses to endothelin-1 and endothelin receptor A subtype (ETA) receptor expression (P < 0.05) and slightly decreased tumor necrosis factor-alpha receptor 1 (TNFRI) expression (P=0.063).Conclusion. Corpora cavernosa from TNF-alpha-infused mice display increased contractile responses and decreased NANC nerve-mediated relaxation associated with decreased eNOS and nNOS gene expression. There changes may trigger ED and indicate that TNF-alpha plays a detrimental role in erectile function. Blockade of TNF-alpha actions may represent an alternative therapeutic approach for ED, especially in pathologic conditions associated with increased levels of this cytokine. Carneiro FS, Zemse S, Giachini FRC, Carneiro ZN, Lima W, Clinton Webb R, and Tostes RC. TNF-alpha infusion impairs corpora cavernosa reactivity. J Sex Med 2009;6(suppl 3):311-319.