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

背景与目的：众所周知，由于剩余小肠中瓜氨酸（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。据报道，一氧化氮（NO）是由L-Arg通过NO合成酶（NOS）合成的，并且NO参与肾脏中血流的调节。我们经历了一个病人与一个非常短的小肠，表现出肾小管间质纤维化（TIF），实验的目的是澄清是否大量小肠切除产生TIF在kidney.Materials和方法：实验研究进行了使用4周龄大鼠90%近端小肠切除术（90%SBR）无论有或没有精氨酸补充6周后手术。结果：在未补充Arg的大鼠中，在90%SBR后6周观察到低血浆Cit和Arg水平、乳清酸尿排泄增加和TIP。血浆氨基酸谱及尿乳清酸排泄增加提示精氨酸缺乏。在90%SBR后补充Arg的大鼠和未补充90%SBR的配对喂养对照大鼠表现出几乎正常的肾小球和肾小管。结果表明：1组大鼠肾组织匀浆中Arg、Cit和NOx（NO2 ^-/NO3 ^-）的含量与对照组相同。结论：大量小肠切除术后肾组织TIF的发生与Arg缺乏有关。精氨酸预防大量小肠切除术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.