Changes in the gastric enteric nervous system and muscle: a case report on two patients with diabetic gastroparesis.
Changes in the gastric enteric nervous system and muscle: a case report on two patients with diabetic gastroparesis.
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DOI：
10.1186/1471-230x-8-21
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发表时间：
2008-05-30
影响因子：
2.4
通讯作者：
Farrugia G
中科院分区：
文献类型：
--
作者：
Pasricha PJ;Pehlivanov ND;Gomez G;Vittal H;Lurken MS;Farrugia G
糖尿病胃轻瘫的病理生理基础知之甚少，很大程度上是由于几乎完全缺乏患者胃神经病理学和分子变化的数据。实验模型表明影响迷走神经、肌肉、肠神经元、Cajal间质细胞（ICC）或其他细胞组分的各种病变。本研究的目的是使用现代分析方法来确定糖尿病胃轻瘫患者胃壁的形态学和分子变化。全层胃活检获得腹腔镜下从两个胃轻瘫患者接受手术干预和从对照组的无病区接受其他形式的胃手术。对样本进行组织学和免疫组织化学检查。虽然这两名患者有严重的难治性症状与营养不良，需要放置胃刺激器，其中一个没有显着的异常相比，控制。该患者症状突然发作，糖尿病持续时间相对较短，控制良好。相比之下，另一名患者长期患有脆性和控制不良的糖尿病，多次发生糖尿病酮症酸中毒和频繁的低血糖发作。组织学检查显示，该患者的肌肉层纤维化增加，神经纤维和肌间神经元显著减少，如PGP9.5染色所评估。此外，在神经元型一氧化氮合酶、血红素加氧酶-2、酪氨酸羟化酶以及c-KIT的染色中观察到显著减少。我们得出结论，不良的代谢控制与胃壁的显著病理变化有关，这些病理变化影响所有主要成分，包括肌肉、神经元和ICC。严重的症状可能发生在没有这些变化，但是，可能反映迷走神经，中枢或激素的影响。因此，胃轻瘫可能是一种异质性疾病。仔细的分子和病理学分析可能允许更精确的表型分化，并深入了解潜在的机制，以及确定新的治疗靶点。
The pathophysiological basis of diabetic gastroparesis is poorly understood, in large part due to the almost complete lack of data on neuropathological and molecular changes in the stomachs of patients. Experimental models indicate various lesions affecting the vagus, muscle, enteric neurons, interstitial cells of Cajal (ICC) or other cellular components. The aim of this study was to use modern analytical methods to determine morphological and molecular changes in the gastric wall in patients with diabetic gastroparesis. Full thickness gastric biopsies were obtained laparoscopically from two gastroparetic patients undergoing surgical intervention and from disease-free areas of control subjects undergoing other forms of gastric surgery. Samples were processed for histological and immunohistochemical examination. Although both patients had severe refractory symptoms with malnutrition, requiring the placement of a gastric stimulator, one of them had no significant abnormalities as compared with controls. This patient had an abrupt onset of symptoms with a relatively short duration of diabetes that was well controlled. By contrast, the other patient had long standing brittle and poorly controlled diabetes with numerous episodes of diabetic ketoacidosis and frequent hypoglycemic episodes. Histological examination in this patient revealed increased fibrosis in the muscle layers as well as significantly fewer nerve fibers and myenteric neurons as assessed by PGP9.5 staining. Further, significant reduction was seen in staining for neuronal nitric oxide synthase, heme oxygenase-2, tyrosine hydroxylase as well as for c-KIT. We conclude that poor metabolic control is associated with significant pathological changes in the gastric wall that affect all major components including muscle, neurons and ICC. Severe symptoms can occur in the absence of these changes, however and may reflect vagal, central or hormonal influences. Gastroparesis is therefore likely to be a heterogeneous disorder. Careful molecular and pathological analysis may allow more precise phenotypic differentiation and shed insight into the underlying mechanisms as well as identify novel therapeutic targets.