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

精氨酸对生长大鼠大面积小肠切除后肾小管间质纤维化作用的研究

• 批准号: 12671734
• 负责人: HEBIGUCHI Tatsuzo
• 金额: $ 1.73万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671734/
• 关键词: short small bowel; renal tubulointerstitial fibrosis; nitric oxide (NO); arginine deficiency; citrulline; microdialysis; focal tubulointerstitial fibrosis

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.

背景与目的：精氨酸(Arg)是大量小肠切除后的必需氨基酸，其原因是残留小肠中瓜氨酸(Cit)的生物合成减少。另有报道称，一氧化氮(NO)是由L-精氨酸通过一氧化氮合酶(NOS)合成的，参与了肾脏血流的调节。我们经历了一例极短的小肠，表现为肾小管间质纤维化(TIF)，本实验旨在阐明大量小肠切除是否会在肾脏产生TIF。材料和方法：4周龄的大鼠接受90%近端小肠切除(90%SBR)，术后6周分别补充或不补充Arg。结果：在不补充Arg的大鼠中，血浆Cit和Arg水平降低，口红排泄增加，TIP在90%SBR后6周出现。血浆氨基转移酶和尿谷氨酸排泄量增加提示精氨酸缺乏。在90%SBR后补充Arg的大鼠和不补充90%SBR的配对喂养的对照组大鼠显示几乎正常的肾小球和肾小管间质。应用微透析技术对肾实质透析后肾组织中Arg、Cit和NOx(N02^-/N03^-)的含量进行分析，提示第1组肾组织中NO的生成与对照组相同。结论：实验研究有力地提示Arg缺乏可导致大量小肠切除后肾脏的TIF。精氨酸预防大量小肠切除后肾小管间质纤维化。

项目成果

蛇口達造: "短腸症候群の栄養管理"医学のあゆみ. 198・13. 1063-1068 (2001)

Tatsuzo Faku：“短肠综合症的营养管理”医学史198・1068（2001）。

蛇口達造, 他: "腸管成長因子としてのアルギニン"小児外科. 32. 133-138 (2000)

Tatsuzo Fukushi 等人：“精氨酸作为肠道生长因子”《小儿外科》32. 133-138 (2000)。

蛇口達造, 他: "新生児期短腸症候群における肝障害"JJPEN. 23. 611-615 (2001)

Tatsuzo Fukushi 等：“新生儿短肠综合征的肝损伤”JJPEN 23. 611-615 (2001)。

蛇口達造: "腸管成長因子としてのアルギニン"小児外科. 32(2). 133-138 (2000)

Tatsuzo Faku：“精氨酸作为肠道生长因子”，《小儿外科》32(2) (2000)。

Hebiguchi T, et al.: "Does arginine become one of gut-trophic substrates (in Japanese)"Jpn J Pediatr Surg. 32. 133-138 (2000)

Hebiguchi T 等人：“精氨酸会成为肠道营养底物之一吗（日语）”Jpn J Pediatr Surg。