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The Expression Of NT-3 And TrkC In Hirschsprung's Disease

Posted on:2008-06-24Degree:MasterType:Thesis
Country:ChinaCandidate:C F HeFull Text:PDF
GTID:2144360215481253Subject:Academy of Pediatrics
Abstract/Summary:PDF Full Text Request
ObjectiveHirschsprung's disease (HD) is one of the most common diseases in the field of pediatric surgery. It affects about 1 in 5000 live births. It is a congenital condition characterized by the absence of ganglion cell in the submucosal and myenteric plexus of the distal bowel. The real pathogenesis is not fully understood until now. Ganglion cell is derived from neural crest through a process of migration, proliferation, differentiation and apoptosis. Any disruption in this process may cause the failure of genesis of the ganglion cell.Neurotrophic factor 3 (NT-3) plays an important role in the enteric nerver system. First, it promotes the development from neural crest-derived cells to neurons or glia. Second, it enhances outgrowth of neurite. Third, it maintains the appearance of neurons. Tyrosine kinase receptor C (TrkC) is its high affinity receptor which can transfer the information of the NT-3. It can be postulated that the NT-3 may have an important role in the development of enteric nerver system. If NT-3 is defective, there will be no enteric neuron within the enteric nerver system. So NT-3 may be one of the factors which participate in the pathogenesis of the HD.The objective of the current study is to analysis the differences in the expression of NT-3 and TrkC among the aganglionic, transitional and normal segments of the HD by Western blot. We want to research the role of NT-3 in the pathogenesis of HD. The samples from the normal segment are taken as the control group and those from the aganglionic and transitional segments are taken as the experimental groups. Materials and methodsEntire resected specimens were obtained from 20 patients (range 26 days-5 years; 4 females and 16 males) with HD at pull-through operation in our hospital. The diagnosis is proved by radiology (barium enema), manometry, pathology in all patients. 16 cases are classified into common type, 1 case into the short segment type and 3 cases into the long segment type. The cytoplasm and menbrance proteins were obtained by physical and chemical methods from the normal, aganglionic and trasitional intestine separately. Western blot analysis was employed to measure the expression levels of NT-3 and TrkC. Results were expressed as mean±standard error of the mean. The data were analyzed by t-test, with the threshold for significance set at P<0.05.ResultsNT-3 is expressed in the normal segment of HD with a obvious brand on the NC whose intensity is 64.08±6.17. There is no NT-3 in the aganglionic and transitional segments with almost no brand on the NC whose intensities are 15.28±3.60and 14.37±2.96 separately. There are significant differences between the experimental groups and the control group( p≤0.05).TrkC is expressed in the normal segment of HD with a obvious brand on the NC whose intensity is 43.94±5.10. There is less TrkC in the transitional segment with a weaker brand on the NC whose intensity is 25.23±2.52. But no NT-3 is expressed in the aganglionic segment with almost no brand on the NC whose intensity is 9.28±1.34. So expression of TrkC is significantly different between the experimental groups and the control group( p≤0.05) in our samples.ConclusionThe expression of NT-3 and TrkC is different in various segments of the HD gut. The defect of NT-3 may participate in the pathogenesis of HD.
Keywords/Search Tags:Hirschsprung's disease, neurotrophic factor 3, tyrosine kinase receptor C, Western blot
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