A STUDY OF ARGININE ACTION ON RENAL TUBULOINTERSTITIAL FIBROSIS AFTER MASSIVE SMALL BOWEL RESECTION IN GROWING RATS

背景与目的：由于残存小肠中瓜氨酸（Cit）的生物合成减少，精氨酸（Arg）在小肠大面积切除后成为必需氨基酸。另据报道，一氧化氮（NO）是由l -精氨酸通过NO合成酶（NOS）合成的，并且NO参与肾脏血流的调节。我们经历了一个非常短的小肠患者，表现为管间质纤维化（TIF），该实验旨在阐明大量小肠切除术是否会在肾脏中产生TIF。材料和方法：实验研究采用4周龄大鼠，术后6周进行90%近端小肠切除（90% SBR），并补充或不补充Arg。结果：在未补充Arg的大鼠中，90% SBR后6周观察到血浆中Cit和Arg水平低，尿中orotate排泄量增加，TIP。血浆氨基图和尿中精氨酸排泄量增加提示存在精氨酸缺乏。90%SBR后补充精氨酸的大鼠和不补充90%SBR的配对喂养的对照大鼠的肾小球和小管间质基本正常。采用微透析技术分析肾实质透析液中Arg、Cit和NO x (N02^-/N03^-)，提示1组和对照组均维持NO的生成。结论：实验研究强烈提示精氨酸缺乏引起大量小肠切除术后肾脏TIF的发生。精氨酸可防止大肠子切除后肾小管间质纤维化。

Background and Aim : It is known that arginine (Arg) becomes an essential amino acid after massive resection of the small bowel due to decreased biosynthesis of citrulline (Cit) in the remaining small bowel. It is also reported that nitric oxide (NO) is synthesized from L-Arg by NO synthase (NOS), and NO is involved in the regulation of blood flow in the kidney. We experienced a patient with an extremely short small bowel, showing tubulointerstitial fibrosis (TIF), The experiment was designed to clarify whether massive small bowel resection produces TIF in the kidney.Materials and Methods: An experimental study was performed using 4-week-old rats with 90% proximal small bowel resection (90% SBR) either with or without Arg supplementation for 6 weeks after surgery.Results: In rats without Arg supplementation, low plasma levels of Cit and Arg, increased urinary excretion of orotate, and TIP was observed 6 weeks after 90% SBR. The data from plasma aminogram, and increased excretion of urinary orotate suggested the presence of Arg deficiency. Rats with Arg supplementation after 90% SBR, and pair-fed control rats without 90%SBR demonstrated almost normal glomeruli and tubulointerstitium. It is suggested that NO production in group 1 is maintained as well as control groups by analyzes of Arg, Cit and NO x (N02^-/N03^-) in diaiysates of renal parenchyma using microdialysis technique.Conclusion: Experimental study strongly suggests that Arg deficiency causes TIF in the kidney after massive small bowel resection. Arginine prevents renal tubulointerstitium from fibrosis after massive small bowel resection.