Shattuck K E, Grinnell C D, Goldman A S, Rassin D K
Department of Pediatrics, University of Texas Medical Branch, Galveston 77555-0526, USA.
J Investig Med. 1996 Feb;44(2):64-9.
TNF-alpha mediates the hepatic response to sepsis by mechanisms which are not well understood. TNF-alpha is known to stimulate the hepatocellular uptake of specific amino acids in vivo; however, little is known about the direct effects of TNF-alpha on hepatic amino acid or glutathione homeostasis, which is a potential factor in the acute hepatic response to sepsis.
Using the isolated perfused rat liver, we characterized the effects of TNF-alpha on the secretion of amino acids and glutathione into bile and perfusate. Livers taken from adult male Sprague-Dawley rats were perfused with TNF-alpha at a dose of 1 or 2 micrograms. Bile and perfusate were collected for the quantitation of amino acid and glutathione concentrations.
Administration of 2 micrograms TNF-alpha resulted in significant increases in biliary and perfusate concentrations of branched chain, gluconeogenic, and total amino acids. TNF-alpha was also associated with dose-related increases in oxygen uptake, and greater biliary concentrations of glutathione.
TNF-alpha has direct effects upon hepatic amino acid metabolism, which represent some of the early events involved in the mechanism of response to sepsis.
肿瘤坏死因子-α（TNF-α）通过尚不完全清楚的机制介导肝脏对脓毒症的反应。已知TNF-α在体内可刺激肝细胞对特定氨基酸的摄取；然而，关于TNF-α对肝脏氨基酸或谷胱甘肽稳态的直接影响却知之甚少，而这是肝脏对脓毒症急性反应中的一个潜在因素。
利用离体灌注大鼠肝脏，我们研究了TNF-α对氨基酸和谷胱甘肽分泌到胆汁和灌注液中的影响。取成年雄性Sprague-Dawley大鼠的肝脏，用1或2微克剂量的TNF-α进行灌注。收集胆汁和灌注液以定量氨基酸和谷胱甘肽浓度。
给予2微克TNF-α导致支链氨基酸、糖异生氨基酸和总氨基酸的胆汁及灌注液浓度显著增加。TNF-α还与氧摄取的剂量相关增加以及胆汁中谷胱甘肽浓度升高有关。
TNF-α对肝脏氨基酸代谢有直接影响，这代表了脓毒症反应机制中涉及的一些早期事件。
