In vivo whole body and organ arginine metabolism during endotoxemia (sepsis) is dependent on mouse strain and gender
In vivo whole body and organ arginine metabolism during endotoxemia (sepsis) is dependent on mouse strain and gender
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DOI：
10.1093/jn/134.10.2768s
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发表时间：
2004-10-01
影响因子：
4.2
通讯作者：
Deutz, NEP
中科院分区：
文献类型：
--
作者：
Luiking, YC;Hallemeesch, MM;Deutz, NEP
精氨酸代谢涉及不同的器官，如肾、肠和肝，它们在器官间轴上共同作用。精氨酸生产的主要途径是蛋白质分解和瓜氨酸重新生产精氨酸；精氨酸的处理主要用于蛋白质合成或被精氨酸酶和一氧化氮合酶（NOS）利用。为了评估正常情况下和内毒素血症期间体内器官精氨酸代谢，我们使用了小鼠模型，并分析了性别和品系差异。采用稳定同位素输注方案，对雄性和雌性近交系FVB和C57BL6/J小鼠进行麻醉和置管，研究其全身、肠道、肝脏、肾脏和肌肉代谢。动物分别用生理盐水或脂多糖处理。血浆精氨酸水平在雌性小鼠中趋于较高，但与雄性小鼠无显著差异（P = 0.09）。C57BL6/J小鼠的全体精氨酸产量和精氨酸清除率有升高趋势（P < 0.1），而FVB小鼠的瓜氨酸（P = 0.05）、NO （P = 0.08）和新生精氨酸（P < 0.01）产量较高。内毒素血症时，FVB小鼠全身精氨酸清除率升高（P < 0.05）， C57BL6/J小鼠全身精氨酸清除率降低（P < 0.01）。在脏器水平上，FVB的门静脉引流脏器（PDV）精氨酸代谢高于C57BL6/J小鼠（P < 0.05）。内毒素血症时，肝脏精氨酸代谢总体下降（P < 0.05），而PDV、肌肉和肾脏精氨酸代谢存在品系差异。总之，稳定同位素技术在多导管小鼠中可以测量全身和器官水平的精氨酸代谢。菌株和性别差异存在于生理条件下和内毒素血症期间的精氨酸代谢。
Arginine metabolism involves various organs such as the kidney, the intestines, and the liver, which act together in an interorgan axis. Major pathways for arginine production are protein breakdown and de novo arginine production from citrulline; disposal of arginine is mainly used for protein synthesis or used by the enzymes arginase and nitric oxide synthase (NOS). To assess in vivo organ arginine metabolism under normal conditions and during endotoxemia we used a mouse model, and analyzed for gender and strain differences. Male and female inbred FVB and C57BL6/J mice were anesthetized and catheterized to study whole body, gut, liver, renal and muscle metabolism, using a stable isotope infusion protocol. Animals were treated with saline or lipopolysaccharide. Plasma arginine levels tended to be higher in female mice, although levels were not significantly different from male mice (P = 0.09). Although not all significantly different, whole body arginine production and arginine clearance tended to be higher in C57BL6/J mice (P < 0.1), while citrulline (P = 0.05), NO (P = 0.08), and de novo arginine (P < 0.01) production were higher in FVB mice. During endotoxemia, NO production increased in general (P < 0.05), while whole body arginine clearance increased in FVB mice, but decreased in C57BL6/J mice (P < 0.01). At the organ level, portal-drained viscera (PDV) arginine metabolism was higher in FVB than in C57BL6/J mice (P < 0.05). During endotoxemia, liver arginine metabolism decreased in general (P < 0.05), while strain differences existed for PDV, muscle, and renal arginine metabolism. In conclusion, stable isotope techniques in multicatheterized mice allow measurements of arginine metabolism on whole body and organ level. Strain and gender differences are present in arginine metabolism under physiological conditions and during endotoxemia.