中高位肛门直肠畸形直肠末端病理改变及神经元特异性烯醇化酶、钙结合蛋白和c-kit的表达

Histomorphological changes and expression of neuron-specific enolase, S-100 protein and c-kit in the terminal rectums in patients with high and intermediate anorectal malformation

目的探讨先天性肛门直肠畸形(ARMs)患儿直肠末端肠壁病理变化及神经发育情况,探讨术后排便功能障碍的发生机制。方法应用苏木素-伊红(HE)染色法、Masson染色、免疫组织化学和Westernblot检测中高位肛门直肠畸形组和正常对照组患儿直肠末端肠壁内各层病理形态改变及神经元特异性烯醇化酶(NSE)、钙结合蛋白(S-100)、c-kit的表达。结果与正常对照组比较,中高位ARMs组中直肠末端肠壁内存在不同程度病理形态改变,包括黏膜炎症、黏膜下脉管扩张,肌层纤维组织增生等;ARMs组直肠末端黏膜下和肌间神经元数目较正常对照组明显减少[(5.30±1.26)个比(1.20±0.73)个,P=0.007];中高位ARMs组中直肠末端肠壁内NSE、S-100和c-kit的表达量均低于正常对照组,蛋白表达量别为(NSE:0.510±0.033比0.476±0.036;S-100:0.445±0.009比0.420±0.012;c-kit:0.982±0.043比0.756±0.017;P=0.023、0.035、0.028)。结论先天性中高位ARMs末端直肠壁组织中存在明显的病理形态学改变,且肠壁内神经节细胞的发育及Cajal间质细胞(ICCs)的分布密度均存在不同程度异常,这可能是中高位ARMs术后排便障碍的重要发生机制之一。

Objective To investigate the morphological changes and development of enteric nerve in terminal rectums in patients with high and intermediate anorectal malformations (ARMs), and to explore the mechanism of bowel dysfunction postoperatively. Methods The hematoxylin and eosin (HE), Masson staining, IHC and Western blotting were used to evaluate the terminal rectums in patients with ARMs and healthy controls. Results Compared with the normal group, the most frequently observed histological finding in mucosa was inflammation and ulcer, submucosal congestion was the most common finding, disrupted muscularis propria and fibrosis was common. The number of submucosal and myenteric plexus also reduced significantly in ARMs group compared with controls (5.30±1.26 vs. 1.20±0.73, P=0.007). The expression levels of neuron-specific enolase (NSE), S-100, and c-kit in ARMs group were significant lower than that in normal group (NSE: 0.510±0.033 vs. 0.476±0.036; S-100: 0.445±0.009 vs. 0.420±0.012; c-kit: 0.982±0.043 vs. 0.756±0.017; P=0.023, 0.035, 0.028, respectively). Conclusion The terminal rectums in ARMs show various specific and non-specific histomorphological changes, along with ganglion cell dysplasia and aganglionosis and reduction of density and distribution of ICC. These findings maybe responsible for the defecation dysfunction after anorectoplasty.