Therapeutic strategy for patients after total excision of large bowel based on pathophysiological mechanism (Establishment of postoperative management after total colectomy).

基于病理生理机制的大肠全切除术后患者的治疗策略（全结肠切除术后管理的建立）。

• 批准号: 09557101
• 负责人: SASAKI Iwao
• 金额: $ 7.74万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09557101/
• 关键词: total colectomy; QDL; hyperaldosteronism; 11betaHSD2; ENaC; Na^+-K^+ ATPase; Ileo-jejunal transposition; Enteroglucagon; Peptide YY; 11B HSD2; E NaC; Na^+-K^+ ATPase; ileo-jejunal transposition(IJT); Peptide YY; 電解質吸収能

[In Rats] We examined function and gene induction relating to the function of aldosteron in small intestinal mucosa and kidney after total proctocolectomy(TPC). Adimnistration of aldosteron evoked amiloride-sensitive short circuit current(Isc) after TPC, otherwise no response of Isc was observed in normal rats. In lower small intestine, TPC induced the activation of 11beta hydroxysteroid dehydrogenase type 2(11beta HSD2) which regulates the function of aldosteron, and alpha, subunit mRNA of amiloride-sensitive epithelial Na+ channel(ENaC). In kidney, 1113 HSD2, alpha beta gamma subunit mRNA of ENaC, and a 1beta1 subunit mRNA of Na+-K+ ATPase were enhanced after TPC.We concluded that hyperaldosteronism is a very important mechanism for the regulation of water and electrolyte balance after total proctocolectomy.[In dogs] Ileal brake, that upper gastrointestinal motility was suppressed by the infusion of nutrients(fat, glucose, etc) into the ileum, has been well recognized. We have conceived the model of Ileo-jejunal transposition(IJT) which is a possible operative procedure to modify this mechanism. We examined the effect of IJT on the motility and transit in normal or totally colectomized dogs. In normal dogs, IJT suppressed postprandial gastric motility and delayed gastric emptying. Plasma enteroglucagon(EG) and Peptide YY(PYY) level were increased in IJT group. In colectomized dogs, IJT delayed gastric emptying and reduced water content of the stool. We conclude that IJT may be a novel operative procedure, which can suppress the upper gastrointestinal motility and improve the quality of life in patients who received total proctocolectomy.

[在大鼠中]我们检测了全直肠切除(TPC)后小肠粘膜和肾脏中与醛固酮功能相关的功能和基因诱导。正常大鼠在TPC后应用醛固酮可诱发阿米洛利敏感短路电流(ISC)，而正常大鼠则无ISC反应。在低位小肠，TPC诱导调节醛固酮功能的11β羟类固醇脱氢酶2(11βHSD2)和阿米洛利敏感的上皮钠通道(ENaC)α亚单位mRNA的激活。在肾脏，1113HSD2、ENaC的α-β-γ亚基和Na+-K+-ATPase的1Beta-1亚单位的mRNA在TPC后显著增加。结论：高醛固酮血症是全结肠切除后调节水和电解质平衡的一个非常重要的机制。回肠制动，通过向回肠内注入营养物质(脂肪、葡萄糖等)而抑制上胃肠运动，已被广泛认识。我们设想了回肠-空肠移位(IJT)模型，这是一种可能的手术方式来改变这一机制。我们观察了IJT对正常或全结肠切除犬的运动和转运的影响。在正常犬中，IJT抑制餐后胃动力和胃排空延迟。IJT组血浆肠高血糖素(EG)和多肽YY(PYY)水平升高。在大肠切除犬模型上，IJT延缓胃排空，减少大便水分含量。我们认为，IJT可能是一种新的手术方式，可以抑制全结肠切除术患者的上胃肠道运动，提高患者的生活质量。

项目成果

N.Otani: "An inhibitory effect of ileo-jejunal transposition on gastric motility in dogs." Journal of GI surgery. (in press).

N.Otani：“回肠空肠转位对狗胃动力的抑制作用。”

K.Koyama: "Induction of epithelial Na+ channel (EnaC) in rat ileum after proctocolectomy" American Journal Physiology. (in press).

K.Koyama：“直肠结肠切除术后大鼠回肠上皮 Na 通道 (EnaC) 的诱导”美国生理学杂志。

内藤広郎: "ヒトにおけるグリセンチンの血中動態" 消化管ホルモン. XV. 20-24 (1997)

Hiroo Naito：“人类高血糖素的血液动力学”胃肠激素 XV。

Kaori Koyama: "Induction of Epithelial Na^+ Channel (ENaC) in Rat Ileum after proctocolecto" American Journal Physiology. In press.

Kaori Koyama：“直肠结肠切除后大鼠回肠上皮 Na^ 通道 (ENaC) 的诱导”美国生理学杂志。