Rice Sarah A, Ten Have Gabriella A M, Engelen Marielle P K J, Deutz Nicolaas E P
Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, AK, United States.
Department of Kinesiology and Sport Management, Texas A&M University, College Station, TX, United States.
Am J Physiol Gastrointest Liver Physiol. 2024 Sep 3;327(5):G673-84. doi: 10.1152/ajpgi.00257.2023.
Human sepsis is characterized by increased protein breakdown and changes in arginine and citrulline metabolism. However, it is unclear whether this is caused by changes in transorgan metabolism. We therefore studied in a induced pig sepsis model the changes in protein and arginine related metabolism on whole body (Wb) and transorgan level. We studied 22 conscious pigs for 18 hours during sepsis, induced by infusing live bacteria ( or after placebo infusion (control). We used stable isotope tracers to measure Wb and skeletal muscle protein synthesis and breakdown, as well as Wb, splanchnic, skeletal muscle, hepatic and portal drained viscera (PDV) arginine and citrulline disposal and production rates. During sepsis, arginine Wb production (p=0.0146), skeletal muscle release (p=0.0035) and liver arginine uptake were elevated (p=0.0031). Wb arginine synthesis, citrulline production, and transorgan PDV release of citrulline, glutamine and arginine did not differ between sepsis and controls. However, Wb (p<0.0001) and muscle (p<0.001) protein breakdown were increased, suggesting that the enhanced arginine production is predominantly derived from muscle breakdown in sepsis. In conclusion, live-bacterium sepsis increases muscle arginine release and liver uptake, mirroring previous pig endotoxemia studies. In contrast to observations in humans, acute live-bacterium sepsis in pigs does not change citrulline production or arterial arginine concentration. We therefore conclude that the arginine dysregulation observed in human sepsis is possibly initiated by enhanced protein catabolism and splanchnic arginine catabolism, while decreased arterial arginine concentration and citrulline metabolism may require more time to fully manifest in patients.
人类脓毒症的特征是蛋白质分解增加以及精氨酸和瓜氨酸代谢的变化。然而，目前尚不清楚这是否是由跨器官代谢的变化引起的。因此，我们在诱导性猪脓毒症模型中研究了全身（Wb）和跨器官水平上蛋白质和精氨酸相关代谢的变化。我们研究了22只清醒猪，在脓毒症期间持续18小时，通过注入活细菌诱导（或在注入安慰剂后作为对照）。我们使用稳定同位素示踪剂来测量全身和骨骼肌蛋白质的合成与分解，以及全身、内脏、骨骼肌、肝脏和门静脉引流内脏（PDV）的精氨酸和瓜氨酸处置及生成速率。在脓毒症期间，精氨酸的全身生成（p = 0.0146）、骨骼肌释放（p = 0.0035）和肝脏精氨酸摄取均升高（p = 0.0031）。脓毒症组和对照组之间的全身精氨酸合成、瓜氨酸生成以及跨器官PDV释放的瓜氨酸、谷氨酰胺和精氨酸没有差异。然而，全身（p < 0.0001）和肌肉（p < 0.001）的蛋白质分解增加，这表明脓毒症中精氨酸生成的增加主要源于肌肉分解。总之，活菌脓毒症增加了肌肉精氨酸释放和肝脏摄取，这与之前猪内毒素血症的研究结果一致。与人类的观察结果相反，猪的急性活菌脓毒症不会改变瓜氨酸生成或动脉血精氨酸浓度。因此，我们得出结论，人类脓毒症中观察到的精氨酸失调可能是由蛋白质分解代谢增强和内脏精氨酸分解代谢引发的，而动脉血精氨酸浓度降低和瓜氨酸代谢可能需要更多时间才能在患者中完全显现出来。
