Yamaoka Ippei, Doi Masako, Nakayama Mitsuo, Ozeki Akane, Mochizuki Shinji, Sugahara Kunio, Yoshizawa Fumiaki
Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory, Naruto, Tokushima 772-8601, Japan.
Am J Physiol Endocrinol Metab. 2006 May;290(5):E882-8. doi: 10.1152/ajpendo.00333.2005. Epub 2005 Dec 13.
The present study was conducted to determine the contribution of muscle protein synthesis to the prevention of anesthesia-induced hypothermia by intravenous administration of an amino acid (AA) mixture. We examined the changes of intraperitoneal temperature (Tcore) and the rates of protein synthesis (K(s)) and the phosphorylation states of translation initiation regulators and their upstream signaling components in skeletal muscle in conscious (Nor) or propofol-anesthetized (Ane) rats after a 3-h intravenous administration of a balanced AA mixture or saline (Sal). Compared with Sal administration, the AA mixture administration markedly attenuated the decrease in Tcore in rats during anesthesia, whereas Tcore in the Nor-AA group became slightly elevated during treatment. Stimulation of muscle protein synthesis resulting from AA administration was observed in each case, although K(s) remained lower in the Ane-AA group than in the Nor-Sal group. AA administration during anesthesia significantly increased insulin concentrations to levels approximately 6-fold greater than in the Nor-AA group and enhanced phosphorylation of eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) and ribosomal protein S6 protein kinase relative to all other groups and treatments. The alterations in the Ane-AA group were accompanied by hyperphosphorylation of protein kinase B and the mammalian target of rapamycin (mTOR). These results suggest that administration of an AA mixture during anesthesia stimulates muscle protein synthesis via insulin-mTOR-dependent activation of translation initiation regulators caused by markedly elevated insulin and, thereby, facilitates thermal accumulation in the body.
本研究旨在通过静脉注射氨基酸(AA)混合物来确定肌肉蛋白质合成对预防麻醉诱导的体温过低的作用。我们检测了清醒(Nor)或丙泊酚麻醉(Ane)大鼠在静脉输注平衡AA混合物或生理盐水(Sal)3小时后,腹腔内温度(Tcore)的变化、蛋白质合成速率(K(s))以及骨骼肌中翻译起始调节因子及其上游信号成分的磷酸化状态。与输注生理盐水相比,输注AA混合物可显著减轻麻醉期间大鼠Tcore的下降,而Nor-AA组的Tcore在治疗期间略有升高。尽管Ane-AA组的K(s)仍低于Nor-Sal组,但在每种情况下均观察到AA给药刺激了肌肉蛋白质合成。麻醉期间输注AA可使胰岛素浓度显著升高至约为Nor-AA组的6倍,并相对于所有其他组和处理增强了真核起始因子4E结合蛋白-1(4E-BP1)和核糖体蛋白S6蛋白激酶的磷酸化。Ane-AA组的这些改变伴随着蛋白激酶B和雷帕霉素哺乳动物靶标(mTOR)的过度磷酸化。这些结果表明,麻醉期间输注AA混合物可通过胰岛素显著升高引起的胰岛素-mTOR依赖性激活翻译起始调节因子来刺激肌肉蛋白质合成,从而促进体内热量蓄积。