Houdijk A P, Teerlink T, Visser J J, van Lambalgen A A, van Leeuwen P A
Department of Surgery, Free University Hospital, Amsterdam, The Netherlands.
Gastroenterology. 1997 Oct;113(4):1375-83. doi: 10.1053/gast.1997.v113.pm9322533.
BACKGROUND & AIMS: Arginine deficiency may underlie the cellular immune depression after surgery in obstructive jaundice, which is associated with gut-derived endotoxemia. The aim of this study was to study arginine metabolism in the bile duct-ligated rat (BDL) after laparotomy.
Treatment with cholestyramine, a known endotoxin binder, was used to evaluate the role of gut-derived endotoxemia.
In BDL rats, arginine levels were lower compared with those in sham-operated controls (P < 0.005), despite a three-fold increase in renal arginine release (P < 0.01). Liver and gut arginine handling also could not explain the reduced arginine levels. Higher plasma arginase activity (P < 0.0001) was measured in BDL rats, explaining both the lower arginine levels (r = 0.73, P < 0.01) and the increase in arginase product levels: ornithine (P < 0.005 and r = 0.72; P < 0.01) and urea (P < 0.01). Cholestyramine treatment prevented the decrease in postoperative arginine deficiency by reducing plasma arginase activity by 43% (P < 0.005). In addition, it significantly lowered plasma levels of the other liver enzymes (aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, and alkaline phosphatase; P < 0.05) in BDL rats.
The study concluded that arginine deficiency in BDL rats after surgery is caused by high plasma liver arginase activity. Cholestyramine prevented the arginine deficiency by reducing plasma arginase activity through the inhibition of additional endotoxin-mediated hepatocellular damage after surgery in BDL rats.
精氨酸缺乏可能是梗阻性黄疸手术后细胞免疫抑制的原因,这与肠道源性内毒素血症有关。本研究的目的是研究剖腹术后胆管结扎大鼠(BDL)的精氨酸代谢。
使用已知的内毒素结合剂消胆胺进行治疗,以评估肠道源性内毒素血症的作用。
与假手术对照组相比,BDL大鼠的精氨酸水平较低(P < 0.005),尽管肾脏精氨酸释放增加了三倍(P < 0.01)。肝脏和肠道对精氨酸的处理也无法解释精氨酸水平的降低。BDL大鼠的血浆精氨酸酶活性较高(P < 0.0001),这既解释了较低的精氨酸水平(r = 0.73,P < 0.01),也解释了精氨酸酶产物水平的增加:鸟氨酸(P < 0.005,r = 0.72;P < 0.01)和尿素(P < 0.01)。消胆胺治疗通过使血浆精氨酸酶活性降低43%(P < 0.005),预防了术后精氨酸缺乏的发生。此外,它还显著降低了BDL大鼠血浆中其他肝酶(天冬氨酸转氨酶、丙氨酸转氨酶、γ-谷氨酰转肽酶和碱性磷酸酶;P < 0.05)的水平。
该研究得出结论,BDL大鼠术后精氨酸缺乏是由血浆肝精氨酸酶活性升高引起的。消胆胺通过抑制BDL大鼠术后额外的内毒素介导的肝细胞损伤,降低血浆精氨酸酶活性,从而预防了精氨酸缺乏。