引用

促红细胞生成素(EPO)通常以其在红细胞生成中的作用而闻名，但也是脊髓运动神经元的一种有效的神经营养/神经保护因子。另一种由缺氧诱导因子-1调控的营养因子，血管内皮生长因子(VEGF)，通过ERK和Akt激活信号引发持久的膈肌运动促进(pMF)。由于EPO也通过ERK和Akt激活发出信号，我们验证了EPO引发类似pMF的假设。使用逆行标记和免疫组化技术，我们在成年雄性Sprague Dawley大鼠中证明EPO及其受体EPO- r在确定的膈运动神经元中表达。鞘内EPO在C4时可诱导持久的pMF;注射后90 min综合膈神经爆发量增加>(注射后90 min基线63 12%;P < 0.001)。EPO增加了ERK的磷酸化(和推测的激活)(1.6倍于对照组;膈运动神经元P < 0.05);EPO还增加了pAkt(1.6倍于对照组; p < 0.05). EPO-induced pMF was abolished by the MEK/ERK inhibitor U0126 [1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto)butadiene] and the phosphatidylinositol 3-kinase/Akt inhibitor LY294002 [2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one], demonstrating that ERK MAP kinases and Akt are both required for EPO-induced pMF. Pretreatment with U0126 and LY294002 decreased both pERK and pAkt in phrenic motor neurons (p < 0.05), indicating a complex interaction between these kinases. We conclude that EPO elicits spinal plasticity in respiratory motor control. Because EPO expression is hypoxia sensitive, it may play a role in respiratory plasticity in conditions of prolonged or recurrent low oxygen.