He C L, Soffer E E, Ferris C D, Walsh R M, Szurszewski J H, Farrugia G
Department of Physiology and Biophysics, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street NW, Rochester, MN 55905, USA.
Gastroenterology. 2001 Aug;121(2):427-34. doi: 10.1053/gast.2001.26264.
BACKGROUND & AIMS: Gastrointestinal complications of long-standing diabetes include nausea, vomiting, abdominal pain, diarrhea, and constipation. The pathophysiology underlying these symptoms is poorly understood. Recent evidence suggests an important role for interstitial cells of Cajal in controlling gastrointestinal motility. The aim of this study was to determine changes in interstitial cells of Cajal and enteric innervation in a patient with insulin-dependent diabetes.
A full thickness jejunal biopsy was obtained from a 38-year-old insulin-dependent diabetic with evidence for diabetic gastroenteropathy. Immunohistochemistry, confocal microscopy, and 3-dimensional reconstruction techniques were used to quantify changes in the volume of interstitial cells of Cajal and enteric innervation.
Interstitial cells of Cajal were markedly decreased throughout the entire thickness of the jejunum. A decrease in neuronal nitric oxide synthase, vasoactive intestinal peptide, PACAP, and tyrosine hydroxylase immunopositive nerve fibers was observed in circular muscle layer while substance P immunoreactivity was increased.
The data suggest that long-standing diabetes is associated with a decrease in interstitial cells of Cajal volume and a decrease in inhibitory innervation, associated with an increase in excitatory innervation. The changes in interstitial cells of Cajal volume and enteric nerves may underlie the pathophysiology of gastrointestinal complications associated with diabetes and suggest future therapeutic targets.
长期糖尿病的胃肠道并发症包括恶心、呕吐、腹痛、腹泻和便秘。这些症状背后的病理生理学机制尚不清楚。最近的证据表明， Cajal间质细胞在控制胃肠动力方面发挥着重要作用。本研究的目的是确定一名胰岛素依赖型糖尿病患者的 Cajal间质细胞和肠内神经支配的变化。
从一名38岁有糖尿病胃肠病证据的胰岛素依赖型糖尿病患者获取全层空肠活检组织。采用免疫组织化学、共聚焦显微镜和三维重建技术来量化 Cajal间质细胞体积和肠内神经支配的变化。
整个空肠全层的 Cajal间质细胞明显减少。在环肌层观察到神经元型一氧化氮合酶、血管活性肠肽、垂体腺苷酸环化酶激活肽和酪氨酸羟化酶免疫阳性神经纤维减少，而P物质免疫反应性增加。
数据表明，长期糖尿病与 Cajal间质细胞体积减少和抑制性神经支配减少有关，同时兴奋性神经支配增加。 Cajal间质细胞体积和肠神经的变化可能是糖尿病相关胃肠道并发症病理生理学的基础，并提示了未来的治疗靶点。
