急性坏死性胰腺炎大鼠中小肠间质Cajal细胞及肌间神经元的损伤导致肠梗阻

Background

Small 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.

 

Methods

ANP 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.

 

Results

L-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).

 

Conclusion

Our results suggest that the pathogenesis of the small intestinal paralysis in ANP may be related to the deficiencies in ICC and nNOS neurons.

学科代码：外科学 整形外科学　　　关键词：急性坏死性胰腺炎