Department of Pediatric Surgery, Xin Hua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
World J Gastroenterol. 2013 Jun 14;19(22):3415-22. doi: 10.3748/wjg.v19.i22.3415.
To investigate the disruptions of interstitial cells of Cajal (ICC) in the remaining bowel in rats after massive small bowel resection (mSBR).
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.
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.
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.
研究大鼠小肠广泛切除（mSBR）后剩余肠段 Cajal 间质细胞（ICC）的破坏情况。
30 只符合纳入标准的雄性 Sprague-Dawley 大鼠随机分为三组（每组 10 只）：A 组大鼠行肠横断再吻合（假手术），术后第 7 天取组织标本；B 组和 C 组大鼠行 80%小肠切除术，B 组大鼠术后第 7 天、C 组大鼠术后第 14 天取组织标本。采用免疫组织化学方法分析小肠组织标本中 ICC 的分布，透射电镜观察 mSBR 后模型大鼠剩余回肠 ICC 的超微结构变化，慢波振荡的细胞内记录评估电起搏。Western 印迹法检测各组肠平滑肌中 c-kit、ICC 表型标志物和膜结合干细胞因子（mSCF）的蛋白表达。
mSBR 后，B 组大鼠 c-kit 阳性细胞数量较假手术组织明显减少，ICC 超微结构发生显著变化伴平滑肌肥大。mSBR 后 7d，剩余肠平滑肌自发性节律性收缩幅度减小（8.5±1.4mV 比 24.8±1.3mV，P=0.037），慢波频率增加（39.5±2.1 次/min 比 33.0±1.3 次/min，P=0.044）。mSBR 后 14d，肠环形平滑肌的收缩功能和电活动恢复正常（幅度 14.9±1.6mV 比 24.8±1.3mV；频率 30.7±1.7 次/min 比 33.0±1.3 次/min）。7d 时 Mscf 和 c-kit 蛋白表达降低（P=0.026），14d 时逐渐恢复正常。ICC 及其相关神经网络被破坏，与 ICC 表型改变有关。
大鼠小肠广泛切除可导致 ICC 网络损伤，ICC 数量减少，引起肠道节律紊乱。mSCF/c-kit 信号通路在 ICC 表型的调节和维持中起作用。
