Intestinal motility immune systems in Hirschsprung's disease model animals

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、高钾和内皮素-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与ETB(/)R的绝对收缩力没有差异。这种肌肉功能肥大在结肠、盲肠和回肠远端无神经节的部分可见，而在回肠近端和空肠的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。

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.