Gu Aiming, Wu Zhihao, Wang Peng, Liu Jun, Wang Jianfeng, Wang Qianqian, Chen Jie
Department of Neurology, Affiliated Hospital of Jiaxing University, Jiaxing, China.
Department of Pediatric Surgery, Xin Hua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Pediatr. 2023 Jan 9;10:975799. doi: 10.3389/fped.2022.975799. eCollection 2022.
To investigate the effect of the distribution and expression of interstitial cells of Cajal (ICCs) and platelet-derived growth factor receptor-α positive (PDGFRα+) cells in different colon segments on colonic motility in children with Hirschsprung disease (HSCR).
Smooth muscles of the narrow and dilated segments of the colon were obtained from 16 pediatric patients with HSCR. The proximal margin was set as the control section. The mRNA and protein expressions of c-Kit, PDGFRα, ANO1, and SK3 channels were examined. Circular smooth muscle strips of the colon were prepared for performing electrophysiology experiments using electric field stimulation (EFS) and intervention from different drugs (TTX, NPPB, Apamin, L-NAME, and CyPPA).
The mRNA and protein expressions of c-Kit, ANO1, PDGFRα, and SK3 were much lower in the narrow segment than those in the dilated and proximal segments of the colon. The narrow segment showed a considerably spontaneous contraction of the muscle strip. After the EFS, the relaxation response decreased from the proximal to the narrow segment, whereas the contraction response increased. TTX blocking did not cause any significant changes in the narrow segment. In contrast, when NPPB, Apamin, L-NAME, and CyPPA were used to intervene in the muscle strips, the proximal segment showed a more sensitive inhibitory or excitatory response than the narrow segment.
Downregulation of the ICCs and PDGFRα+ cells from the proximal to narrow segment may be responsible for the dysmotility of the colon in pediatric HSCR.
探讨先天性巨结肠（HSCR）患儿不同结肠段中Cajal间质细胞（ICCs）和血小板衍生生长因子受体α阳性（PDGFRα+）细胞的分布及表达对结肠动力的影响。
从16例HSCR患儿获取结肠狭窄段和扩张段的平滑肌。将近端边缘设为对照段。检测c-Kit、PDGFRα、ANO1和SK3通道的mRNA和蛋白表达。制备结肠环形平滑肌条，使用电场刺激（EFS）并给予不同药物（TTX、NPPB、Apamin、L-NAME和CyPPA）干预以进行电生理实验。
结肠狭窄段中c-Kit、ANO1、PDGFRα和SK3的mRNA和蛋白表达远低于扩张段和近端段。狭窄段肌条出现明显的自发收缩。EFS后，从近端到狭窄段，舒张反应降低，而收缩反应增强。TTX阻断在狭窄段未引起任何显著变化。相反，当使用NPPB、Apamin、L-NAME和CyPPA干预肌条时，近端段比狭窄段表现出更敏感的抑制或兴奋反应。
从近端到狭窄段ICCs和PDGFRα+细胞的下调可能是小儿HSCR结肠动力障碍的原因。
