Original Article
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jun 14, 2013; 19(22): 3415-3422
Published online Jun 14, 2013. doi: 10.3748/wjg.v19.i22.3415
Disruption of interstitial cells of Cajal networks after massive small bowel resection
Jie Chen, Lei Du, Yong-Tao Xiao, Wei Cai
Jie Chen, Lei Du, Wei Cai, Department of Pediatric Surgery, Xin Hua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
Jie Chen, Department of Pediatric Surgery, School of Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Yong-Tao Xiao, Wei Cai, Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute of Pediatric Research, Shanghai Jiaotong University, Shanghai 200092, China
Author contributions: Chen J and Cai W designed the research; Chen J and Du L performed the research; Xiao YT analyzed the data; Chen J wrote the paper.
Supported by Grants from the Program for Innovative Research Team of Shanghai Municipal Education Commission and Special Foundation of Shanghai Municipal Public Health Bureau, LJ06021; the National Natural Science Foundation of China, No. 30772270, 30972427; and the Scientific Foundation of Nantong University, No. 10Z046
Correspondence to: Wei Cai, MD, PhD, Department of Pediatric Surgery, Xin Hua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kong Jiang Road, Shanghai 200092, China. caiw204@yahoo.com.cn
Telephone: + 86-21-65790000 Fax: +86-21-65011627
Received: December 15, 2012
Revised: February 22, 2013
Accepted: April 13, 2013
Published online: June 14, 2013

AIM: To investigate the disruptions of interstitial cells of Cajal (ICC) in the remaining bowel in rats after massive small bowel resection (mSBR).

METHODS: Thirty male Sprague-Dawley rats fitting entry criteria were divided randomly into three experimental groups (n = 10 each): Group A rats underwent bowel transection and re-anastomosis (sham) and tissue samples were harvested at day 7 post-surgery. Group B and C rats underwent 80% small bowel resection with tissue harvested from Group B rats at day 7 post-surgery, and from Group C rats at day 14 post-surgery. The distribution of ICC at the site of the residual small bowel was evaluated by immunohistochemical analysis of small intestine samples. The ultrastructural changes of ICC in the remnant ileum of model rats 7 and 14 d after mSBR were analyzed by transmission electron microscopy. Intracellular recordings of slow wave oscillations were used to evaluate electrical pacemaking. The protein expression of c-kit, ICC phenotypic markers, and membrane-bound stem cell factor (mSCF) in intestinal smooth muscle of each group were detected by Western blotting.

RESULTS: After mSBR, immunohistochemical analysis indicated that the number of c-kit-positive cells was dramatically decreased in Group B rats compared with sham tissues. Significant ultrastructural changes in ICC with associated smooth muscle hypertrophy were also observed. Disordered spontaneous rhythmic contractions with reduced amplitude (8.5 ± 1.4 mV vs 24.8 ± 1.3 mV, P = 0.037) and increased slow wave frequency (39.5 ± 2.1 cycles/min vs 33.0 ± 1.3 cycles/min, P = 0.044) were found in the residual intestinal smooth muscle 7 d post mSBR. The contractile function and electrical activity of intestinal circular smooth muscle returned to normal levels at 14 d post mSBR (amplitude, 14.9 ± 1.6 mV vs 24.8 ± 1.3 mV; frequency, 30.7 ± 1.7 cycles/min vs 33.0 ± 1.3 cycles/min). The expression of Mscf and c-kit protein was decreased at 7 d (P = 0.026), but gradually returned to normal levels at 14 d. The ICC and associated neural networks were disrupted, which was associated with the phenotype alterations of ICC.

CONCLUSION: Massive small bowel resection in rats triggered damage to ICC networks and decreased the number of ICC leading to disordered intestinal rhythmicity. The mSCF/c-kit signaling pathway plays a role in the regulation and maintenance of ICC phenotypes.

Keywords: Interstitial cells of Cajal, c-kit, Slow wave, Massive small bowel resection, Intestinal dysfunction

Core tip: Several gastrointestinal motility diseases are associated with altered numbers of interstitial cells of Cajal (ICC). Short bowel syndrome is also characterized by disordered intestinal motility immediately after surgery. We have investigated the alterations in numbers and functional changes of ICC that occur as a result of short bowel syndrome. In summary, our study showed modifications of the ultrastructure morphology of ICC, altered numbers of ICC and subsequent altered electrophysiological functional activity in the ileum after massive small bowel resection. However, the association between motility disorders and the changes of ICC should be further evaluated.