Bumetanide, an Inhibitor of NKCC1 (Na-K-2Cl Cotransporter Isoform 1), Enhances Propofol-Induced Loss of Righting Reflex but Not Its Immobilizing Actions in Neonatal Rats.
Bumetanide, an Inhibitor of NKCC1 (Na-K-2Cl Cotransporter Isoform 1), Enhances Propofol-Induced Loss of Righting Reflex but Not Its Immobilizing Actions in Neonatal Rats.
复制标题
NKCC1的抑制剂（Na-K-2CL共转运蛋白同工型1）增强了丙泊酚诱导的骨质反射丧失，但没有固定在新生儿大鼠中的作用。
DOI：
10.1371/journal.pone.0164125
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Goto T
中科院分区：
文献类型：
--
作者：
Koyama Y;Andoh T;Kamiya Y;Miyazaki T;Maruyama K;Kariya T;Goto T
γ -氨基丁酸（GABA）通过增加Na+- k +- 2cl -共转运体异构体1 （NKCC1）的表达而诱导未成熟神经元兴奋，并且GABA能信号从兴奋性到抑制性的转变发生在大鼠出生前，并根据阳离子-氯共转运体表达的发育变化向体侧传播。我们之前的研究表明，与青春期大鼠相比，咪达唑仑以依赖nkcc1的方式激活了新生大鼠的海马CA3区，并诱导了更少的镇静。在本研究中，我们验证了一个假设，即异丙酚诱导的翻正反射丧失（LORR）而非固定动作是由nkcc1依赖机制调节的，并且在新生大鼠中与青春期大鼠相比减少了。我们通过磷酸化环腺苷单磷酸反应元件结合蛋白（pCREB）的免疫染色，估计了在异丙酚给药后，有或没有bumetanide（一种NKCC1抑制剂）的大脑皮层、海马和丘脑的神经元活性。我们研究了布美他尼对出生后7天和28天（P7和P28）大鼠异丙酚诱导的LORR和固定化作用的影响。pCREB在皮质（P = 0.001）和海马（P = 0.01）中的表达量在P = 7时明显高于丙泊酚加布美他尼组。异丙酚诱导的LORR或固定化效应在P7和P28之间没有显著差异。布美他尼显著增强异丙酚诱导的P7大鼠的LORR (P = 0.031)，但对固定化无显著影响。这些结果部分符合我们的假设。他们认为异丙酚可能激活依赖于NKCC1的吻侧中枢神经系统，而不是尾侧中枢神经系统，这些不同的作用可能是在新生大鼠中观察到的镇静和固定作用的不同特性的基础。
Gamma-aminobutyric acid (GABA) has been shown to induce excitation on immature neurons due to increased expression of Na+-K+-2Cl- co-transporter isoform 1 (NKCC1), and the transition of GABAergic signaling from excitatory to inhibitory occurs before birth in the rat spinal cord and spreads rostrally according to the developmental changes in cation-chloride co-transporter expression. We previously showed that midazolam activates the hippocampal CA3 area and induces less sedation in neonatal rats compared with adolescent rats in an NKCC1-dependent manner. In the present study, we tested the hypothesis that propofol-induced loss of righting reflex (LORR) but not immobilizing actions are modulated by NKCC1-dependent mechanisms and reduced in neonatal rats compared with adolescent rats. We estimated neuronal activity in the cortex, hippocampus and thalamus after propofol administration with or without bumetanide, an NKCC1 inhibitor, by immunostaining of phosphorylated cyclic adenosine monophosphate-response element binding protein (pCREB). We studied effects of bumetanide on propofol-induced LORR and immobilizing actions in postnatal day 7 and 28 (P7 and P28) rats. The pCREB expression in the cortex (P = 0.001) and hippocampus (P = 0.01) was significantly greater in the rats receiving propofol only than in the rats receiving propofol plus bumetanide at P 7. Propofol-induced LORR or immobilizing effects did not differ significantly between P7 and P28. Bumetanide significantly enhanced propofol-induced LORR (P = 0.031) but not immobilization in P7 rats. These results are partially consistent with our hypothesis. They suggest that propofol may activate the rostral but not caudal central nervous system dependently on NKCC1, and these differential actions may underlie the different properties of sedative and immobilizing actions observed in neonatal rats.
登录
查看更多内容
影响因子：
5.6
作者：
Puskarjov M;Kahle KT;Ruusuvuori E;Kaila K
通讯作者：
Kaila K
影响因子：
3.7
作者：
Cleary RT;Sun H;Huynh T;Manning SM;Li Y;Rotenberg A;Talos DM;Kahle KT;Jackson M;Rakhade SN;Berry G;Jensen FE
通讯作者：
Jensen FE
影响因子：
16.2
作者：
Glykys J;Dzhala VI;Kuchibhotla KV;Feng G;Kuner T;Augustine G;Bacskai BJ;Staley KJ
通讯作者：
Staley KJ
影响因子：
2.5
作者：
Beloozerova, IN;Sirota, MG;Deliagina, TG
通讯作者：
Deliagina, TG
影响因子：
2.7
作者：
Musienko, P. E.;Zelenin, P. V.;Deliagina, T. G.
通讯作者：
Deliagina, T. G.