肠神经发育异常在先天性胆总管囊肿发病机制中的作用

Role of enteric nervous abnormalities in pathogenesis of congenital choledochal cyst

目的检测肠神经在先天性胆总管囊肿（CCC）中的发育异常，探讨CCC发病机制。方法2007年至2009年连续36例CCC患儿实施胆总管囊肿切除、肝管空肠吻合术，分别切取其远、近端囊壁为实验组；选取计划外怀孕，中晚期终止妊娠胎儿15例的肝外胆道为对照组。对比两组神经生长因子（NGF）及其受体（p^75NGFR和TrkA）、神经细胞特异性烯醇化酶（NSE）和蛋白基因产物S-100、cajal间质细胞（c—kit）和突触素（SY）的表达，分析各指标间以及其与囊肿直径的相关性，明确胆道神经发育与CCC发病关系。结果CCC组各指标在囊肿远端表达均弱于近端表达（F=2．694、2．667、1．833、1．750、1．667、2．139、0．861，P〈0．05）。囊肿远端与胎儿胆管间除SY外差异均有统计学意义（F=2．734、3．552、3．448、2．996、3．337、3．155，P〈0．05）；囊肿近端与胎儿胆管间除TrkA、S-100外，其余指标差异均无统计学意义（F=0．040、0．885、1．246、1．016、0．242，P〉0．05）。囊肿直径与囊肿远端NGF、NSE、S-100、c-kit表达均呈负相关（r1=-0．739、-0．787、-0．577、-0．798，P〈0．05），囊肿远端NGF与P^75NGFR、NSE、S-100、c-kit间，P^75NGFR、NSE、S-100与c-kit间，NSE与S-100间均呈正相关（P〈0．05）。结论胚胎期各种原因导致胆管远端肠神经细胞发育、成熟和分布受限，加之神经．肌肉的传导不良，可导致CCC发病；胆道远端肠神经细胞的发育、分布及神经传导与囊肿大小密切相关。

Objective To explore the pathogenesis of congenital choledochal cysts （CCC） by detecting enteric neural abnormalities in CCC. Methods From 2007 to 2009, 36 children with CCC underwent choledochal cyst excision and hepaticojejunostomy. Their proximal and distal cystic wall specimens were incised respectively and selected as the experimental group. At the same time, the extrahepatic bile ducts of 15 fetus who were late terminated because of unplanned pregnancy were selected as the control group. The expression of NGF and its receptors （P^75NGFR and TrkA）, NSE, S-100, Cajal interstitial cells and SY between two groups were compared and the correlation between each index and cysts＇ diameters was analyzed in order to understood the relationship between the pathogenesis of CCC and neural abnormalities. Results The expression levels of all indicators in the distal cysts were weaker than those in the proximal ones （F = 2. 694, 2. 667, 1. 833, 1. 750, 1. 667, 2. 139, 0. 861,P 〈 0. 05）. There was significant difference in the expression of indicators except SY between distal cysts and fetal bile ducts （ F = 2. 734, 3. 552, 3. 448, 2. 996, 3. 337, 3. 155 ,P 〈0.05 ） ; There was no significant difference between the proximal cysts and fetal bile ducts except TrkA and S-100 （ F = 0. 040, 0. 885, 1. 246, 1. 016, 0. 242, P 〉 0. 05 ）. The expression of NGF, NSE, S-100 and c-kit in distal cysts had a negative correlation with the diameter of cysts （ r= - 0. 739, - 0. 787, - 0. 577, - 0. 798,P 〈 0. 05） ; There was a positive correction between the expression of NGF with p^75NCFR, NSE, S-100 and c-kit in distal cysts （P 〈 0. 05）, between the expression of c-kit with P^75NGFR, NSE, S-100, as well as between the expression of NSE with S-100. Conclusion The restriction of enteric nerve distribution and maturation in distal biliary tract, coupled with nerve-muscle transmission badness due to embryonic dysplasia may cause CCC. The size of cyst is closely related to the upgrowth, distribution and nerve conduction of enteric nerve cells in distal biliary tract.