Muscularis inflammation and the loss of interstitial cells of Cajal in the endothelin ETB receptor null rat
Muscularis inflammation and the loss of interstitial cells of Cajal in the endothelin ETB receptor null rat
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DOI：
10.1152/ajpgi.00077.2004
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发表时间：
2004-09-01
影响因子：
4.5
通讯作者：
Ozaki, H
中科院分区：
文献类型：
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作者：
Suzuki, T;Won, KJ;Ozaki, H
内皮素受体缺失大鼠[ETB(-/-)]是一种长节段先天性巨结肠的动物模型。这些动物在胃肠道狭窄区域附近有明显的肠胀(巨肠)，缺乏肠神经节。进行实验以确定在这些动物中发生的病理生理变化，并检查肌层作为一个独特的、具有免疫活性的隔室。我们观察到ETB(-/-)大鼠的肠道菌群异常，其中包括小肠膨胀区的革兰氏阴性需氧菌(肠杆菌科)和厌氧菌(类杆菌科)的显著增加。组织化学观察显示，中性粒细胞少见或未见中性粒细胞浸润，但肌层内ED2阳性巨噬细胞数量增多。肌层IL-1β和IL-6mRNA表达显著增加，CD14(内毒素受体)水平显著增加。ETB(-/-)大鼠扩张肠区自发时相收缩呈不规则变化，这与巨噬细胞数量增多和Cajal间质细胞(ICC)损伤有关。这些结果提示ED2阳性的滞留巨噬细胞可能在ETB(-/-)大鼠肌层炎症中起重要作用。巨噬细胞的数量增加和激活可能导致ICC网络的破坏，导致肌间神经节完整的肠道区域的肠道节律紊乱。
Endothelin receptor null rats [ETB(-/-)] are a model for long-segment Hirschsprung's disease. These animals have significant intestinal distension (megaileum) proximal to a constricted region of the gastrointestinal tract lacking enteric ganglia. Experiments were performed to determine the pathophysiological changes that occur in these animals and to examine the tunica muscularis as a unique, immunologically active compartment. We observed abnormal intestinal flora in ETB(-/-) rats, which included a marked increase in gram-negative aerobes (Enterobacteriaceae) and anaerobes (Bacteroidaceae) in the distended region of the small intestine. Histochemical observations showed that neutrophilic infiltration was rarely or not observed, but the number of ED2 positive macrophages was increased in the tunica muscularis. Expression of IL-1beta and IL-6 mRNA was also significantly increased, and the level of CD14 (LPS receptors) were increased significantly in the tunica muscularis. Spontaneous phasic contractions were irregular in the distended intestinal regions of ETB(-/-) rats, and this was associated with an increased number of macrophages and damage to interstitial cells of Cajal (ICC) as revealed by using Kit-like immunoreactivity and electron microscopy. These results suggest that ED2-positive resident macrophages may play an important role in the inflammation of tunica muscularis in ETB(-/-) rats. Increased numbers and activation of macrophages may result in damage to ICC networks leading to disordered intestinal rhythmicity in regions of the gut in which myenteric ganglia are intact.