Intestinal motility immune systems in Hirschsprung's disease model animals

先天性巨结肠模型动物的肠道运动免疫系统

• 批准号: 12460132
• 负责人: OZAKI Hiroshi
• 金额: $ 9.28万
• 依托单位: THE UNIVERSITY OF TOKYO
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 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/en/grant/KAKENHI-PROJECT-12460132/
• 关键词: Hirschsprung's disease; motility; contraction; morphology; endothelin B receptor; smooth muscle; megaileum; NO; 腸; 炎症; 平滑筋; 収縮性

The endothelin ETB receptor null rat (ETB(-/-)R) has an intestinal segment without ganglia, and this rat is characterized by an intestinal obstruction similar to those observed in human Hirschsprung' s disease. In the present study, we have examined the myogenic mechanism responsible for the obstruction in the ETB(-/-)R.The ETB(-/-)R has an enlarged belly and the average life span was 18.1 day. The bowel from the rectum to the lower part of the small ileum, was constricted whereas the upper region was dilated with fecal stasis and thus presented megaileum. The constricted muscle segments without ganglia had a greater increase in absolute force when stimulated by carbachol, high K+, and endothelin-1 comparing to that of normal siblings. In contrast, in the dilated part with ganglia, the absolute contractile force due to these stimulants in the ETB(-/-)R was not different from that in the ETB(+/+)R. Such a functional hypertrophy of the musculature was observed in the parts of the colon, caecum, and distal ileum without ganglia, but not in the part of the proximal ileum and jejunum with ganglia. Morphological study demonstrated that the thickness of the circular and longitudinal muscle layers was greater in the constricted part of the intestine in the ETB(-/-)R, and these changes were associated with an increase in the number of smooth muscle cells.The above findings suggest that both the increased contractility of smooth muscle and the increased thickness of the intestinal muscular wall may contribute to the intestinal obstruction in the ETB(-/-)R.

ETB受体缺失大鼠(ETB(-/-)R)有一个无神经节的肠段，其肠梗阻特征与人类先天性巨结肠症的S病相似。在本研究中，我们探讨了导致ETB(-/-)R梗阻的肌源性机制。ETB(-/-)R的腹部较大，平均寿命为18.1天。从直肠到小回肠下部的肠管收缩，上部扩张，伴有粪便淤滞，出现巨回肠。在卡巴胆碱、高K+和内皮素-1的刺激下，无神经节的收缩肌段的绝对力比正常同胞的增加更大。相反，在有神经节的扩张部分，ETB(-/-)R和ETB(+/+)R对这些兴奋剂的绝对收缩力没有差异。这种肌肉功能肥大在无神经节的结肠、盲肠和回肠远端可见，而在回肠近端和空肠有神经节的部分则未见。形态学研究表明，ETB(-/-)R的环状肌层和纵向肌层厚度较大，且这些变化与平滑肌细胞数量的增加有关。上述结果提示，ETB(-/-)R的肠梗阻可能与平滑肌的收缩能力增加和肠壁厚度的增加有关。

项目成果

S.-C.Kwon, H.Ozaki, H.Karaki: "Mechanisms of the inhibitory effect of NO donor, sodium nitroprusside, on excitation-contraction coupling in guinea-pig taenia coli"Am. J. Physiol.. 279. G1235-G1241 (2000)

S.-C.Kwon、H.Ozaki、H.Karaki：“NO 供体硝普钠对豚鼠大肠杆菌兴奋-收缩耦合的抑制作用机制”Am。

S.Torihashi ら: "Resident macrophages activated by lipopolysaccharide (LPS) suppress muscle tension and initiate inflammatory response in the gastrointestinal muscle layer.,"Histochemistry & Cell Biology. 113. 73-80 (2000)

S. Torihashi 等人：“脂多糖 (LPS) 激活的驻留巨噬细胞抑制胃肠道肌肉层中的肌肉紧张和炎症反应。”，《组织化学与细胞生物学》113. 73-80 (2000)。

S. -C. Kwon, H. Ozaki and H. Karaki: "Mechanisms of the inhibitory effect of NO donor, sodium nitroprusside, on excitation-contraction coupling in guinea-pig taenia coli"Am. J. Physiol.. 279. G1235-G1241

S.-C。

M.Hori ら: "Up-regulation of inducible nitric oxide synthase by autocrine action of prostaglandins in the LPS-treated resident macrophage in the intestinal muscle layer."Am.J.Physiol.. (印刷中). (2001)

M.Hori 等人：“通过 LPS 处理的肠道肌肉层驻留巨噬细胞中前列腺素的自分泌作用上调诱导型一氧化氮合酶。”Am.J.Physiol..（出版中）。

S.Torihashi, M.Hori, H.Ozaki: "Macrophages in muscle layer of gastrointestinal tract : Impairment of muscle contraction by treatment with lipopolysaccharide"Acta. Histochem. Cytochem.. 34. 219-222 (2001)

S.Torihashi、M.Hori、H.Ozaki：“胃肠道肌肉层中的巨噬细胞：脂多糖治疗对肌肉收缩的损害”Acta。