Damage of the interstitial cells of Cajal and myenteric neurons causing ileus in acute necrotizing pancreatitis rats.
Damage of the interstitial cells of Cajal and myenteric neurons causing ileus in acute necrotizing pancreatitis rats.
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DOI：
10.1016/j.surg.2010.04.023
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发表时间：
2011-02
期刊：
影响因子：
3.8
通讯作者：
Hui Zhou;Li Liu;Yu Bai;Wenbin Wu;Gui-xiang Li;Jianping Li;D. Zou;Jun Gao;Zhaoshen Li
中科院分区：
文献类型：
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作者：
Hui Zhou;Li Liu;Yu Bai;Wenbin Wu;Gui-xiang Li;Jianping Li;D. Zou;Jun Gao;Zhaoshen Li
背景急性坏死性胰腺炎(ANP)患者的小肠动力受损。本研究旨在检测实验性急性胰腺炎时小肠运动功能的损害，并探讨Cajal间质细胞、肌间神经元在肠梗阻发病机制中的作用及相关机制。方法采用30%L-鸟氨酸3g/kg，每小时一次腹腔注射诱发急性胰腺炎。观察ANP诱发24小时后小肠电活动移行性肌电复合波(MMCs)和慢波的变化。采用脏器浴法观察大鼠自主机械活动及对乙酰胆碱、氯化钾、河豚毒素和一氧化氮合酶抑制剂L的收缩反应，并用c-Kit、PGP9.5和一氧化氮合酶标记物分别观察ICC、肌间神经元和神经元型一氧化氮合酶免疫反应细胞网络的形态变化。结果鸟氨酸诱导的坏死性胰腺炎表现为多种症状，包括小肠平滑肌自发性收缩幅度降低，体外对ACh、TTX和L-NNA的收缩反应减弱，MMC周期中断，体内慢波的主频和主功率降低。此外，形态学研究还证实了ICC(ANP组与对照组；P=.000)、肌间神经元(ANP组与对照组；P=0.001)和nNOS免疫反应神经元(ANP组与对照组；P=.000)的损伤。ANP大鼠小肠肌层nNOS蛋白表达明显减少(ANP组与对照组比较，P=0.032)。结论ANP小肠麻痹的发生可能与ICC和nNOS神经元的缺失有关。
BACKGROUNDSmall intestinal motility is impaired in acute necrotizing pancreatitis (ANP). The present study was designed to detect the impairment in small intestinal motility and to assess the role of interstitial cells of Cajal (ICC), myenteric neurons and the associated mechanism in the pathogenesis of ileus during experimentally induced acute pancreatitis.METHODSANP was induced by intraperitoneal injections of 30% L-ornithine at a dose of 3 g/kg at hourly intervals. The alterations of small intestine electrical activity—migrating myoelectric complexes (MMCs), and slow waves—were measured 24 hr after ANP induction. The spontaneous mechanical activity and the contractile response to ACh, KCl, tetrodotoxin (TTX) and the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine (L-NNA) were evaluated by organ bath technique, and the morphologic alterations of the network of ICC, myenteric neurons and neuronal nitric oxide synthase (nNOS) immunoreactive cells were evaluated using the markers of c-Kit, PGP9.5, and nNOS, respectively. To demonstrate the deficiencies in enteric neuronal origin, we also measured nNOS expression in the muscular layer of ileum.RESULTSL-ornithine–induced necrotizing pancreatitis manifests with multiple symptoms, including decreased amplitude of spontaneous contractions in small intestinal smooth muscle, declined contractile response to ACh, TTX, and L-NNA in vitro, disrupted MMC cycle length, decreased dominant frequency and dominant power of slow waves in vivo. Furthermore, the morphologic studies demonstrated the damage of ICC (ANP group versus control; P = .000), myenteric neurons (ANP group versus control; P = .001) and nNOS immunoreactive neurons (ANP group versus control; P = .000). We also observed a substantial loss in the expression of nNOS protein in muscular layer of the small intestine (ANP group versus control; P = .032).CONCLUSIONOur results suggest that the pathogenesis of the small intestinal paralysis in ANP may be related to the deficiencies in ICC and nNOS neurons.