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先天性巨结肠肠壁Cx43蛋白和Cajal间质细胞的分布
Distribution of connexin 43 and interstitial cells of Cajal in bowels of children with Hirschsprung's disease
目的：观察缝隙连接蛋白43（Cx43）及Cajal 间质细胞(ICC)在先天性巨结肠(HD)肠壁中的分布，探讨Cx43和ICC与HD发病的关系。方法：运用免疫组织化学方法观察42例经病理诊断为HD的肠壁标本内各层之间Cx43蛋白和ICC的分布情况，其中男33例，女9例（年龄2个月至10岁），实验标本均为散发病例，全部取材经组织病理学检测符合HD诊断，包括常见型30例，短段型12例，并取5例肠套叠患儿（30 d至8岁，男4例，女1例）作为对照组。结果：HD狭窄段(无神经节细胞肠段)肠壁肌层内Cx43和ICC表达缺失，各层中几乎未见Cx43表达和ICC分布，与HD扩张段（有神经节细胞肠段）及正常对照组之间的差异有显著性意义(P<0.01)。HD移行段肠壁Cx43和ICC有中等强度表达，与扩张段、狭窄段之间差异有显著性(P<0.01)。HD扩张段肠壁Cx43和ICC呈强阳性分布，黏膜下层和纵肌层未见或少见Cx43表达。HD扩张段和正常对照组肠壁内Cx43和ICC表达差异无显著性。结论：Cx43表达缺失或减少、缝隙连接结构的破坏及ICC结构、分布异常，导致细胞间物质、电信号的传递障碍，可能是HD发病的原因之一。［中国当代儿科杂志，2009，11（3）：213-216］
OBJECTIVE: To investigate the distribution of connexin 43 (Cx43) and interstitial cells of Cajal (ICC) in bowels of children with Hirschsprung's disease (HD) and explore their roles in the pathogenesis of HD. METHODS: Forty-two children with HD diagnosed by histopathology (33 males and 9 females) aged from 2 months to 10 years were enrolled. Expression of Cx43 and ICC in the bowels was detected using immunohistochemistry. These cases were all sporadic, including 30 cases of common type and 12 cases of short segment type. Five samples from the children with intussusception (aged from 1 month to 8 years) were used as controls. RESULTS: Cx43 and ICC were not expressed in the muscle layers of the aganglionic segment in children with HD, which was significantly different from the Cx43 and ICC expression in the ganglionic segment of HD patients and the control bowels. Moderate expression of Cx43 and ICC were observed in the migratory segment, which was significantly different from that in the ganglionic and aganglionic segments in patients with HD. Moderate or strong expression of Cx43 and ICC was observed in the circular muscle and the region between the circular and longitudinal layer in the ganglionic segment from patients with HD. There were no significant differences in the Cx43 and ICC expression between the ganglionic segment of HD patients and control bowels. CONCLUSIONS: The absence of Cx43 and ICC expression in the aganglionic bowel and the destruction of the gap junction may induce the dysfunctions of intercellular substance exchange and communication transmission, which might partly be responsible for the pathogenesis of HD.［Chin J Contemp Pediatr, 2009, 11 (3):213-216］
先天性巨结肠 / 缝隙连接蛋白 / Cajal 间质细胞 / 免疫组织化学 / 儿童
［1］de Lorijn F, Boeckxstaens GE, Benninga MA. Symptomatology, pathophysiology, diagnostic work-up, and treatment of Hirschsprung disease in infancy and childhood［J］.Curr Gastroenterol Rep, 2007, 9(3):245-253.
［2］Burns AJ. Disorders of interstitial cells of Cajal［J］. J Pediatr Gastroenterol Nutr, 2007, 45(Suppl 2):S103-106.
［3］乔颜春，孙青. 连接蛋白Connexin43的研究进展［J］. 国际病理科学与临床杂志, 2005, 25(4)：345-347.
［4］张华，李仲荣，朱利斌，陈聪德，谢小志，谢丽微.先天性巨结肠肠壁S-100蛋白的表达和神经元型一氧化氮合酶阳性神经的异常分布［J］.实用儿科临床杂志, 2006, 21（12）：793-794.
［5］Amiel J, Sproat-Emison E, Garcia-Barcelo M, Lantieri F, Burzynski G, Borrego S. Hirschsprung disease, associated syndromes and genetics: a review［J］. J Med Genet, 2008, 45(1):1-14.
［6］Heanue TA, Pachnis V. Enteric nervous system development and Hirschsprung′s disease: advances in genetic and stem cell studies［J］. Nat Rev Neurosci, 2007, 8(6):466-479.
［7］Kessmann J. Hirschsprung′s disease: Diagnosis and management［J］. Am Fam Physician, 2006, 74(8):1319-1322.
［8］Cottrell GT, Burt JM. Functional consequences of heterogeneous gap junction channel formation and its influence in health and disease［J］. Biochim Biophys Acta, 2005, 1711(2):126-141．
［9］Kitamura Y, Hirota S, Nishida T. A loss-of-function mutation of c-kit results in depletion ofmast cells and interstitial cells of Cajal, while its gain-of-function mutation results in their oncogenesis［J］. Mut Res, 2001, 477(4):165-171.
［10］Lorincz A, Redelman D, Horváth VJ, Bardsley MR, Chen H, Ordog T. Progenitors of interstitial cells of cajal in the postnatal murine stomach［J］. Gastroenterology, 2008, 134(4):1083-1093.
［11］Horváth VJ, Vittal H, Lorincz A, Chen H, Almeida-Porada G, Redelman D, et al. Reduced stem cell factor links smooth myopathy and loss of interstitial cells of cajal in murine diabetic gastroparesis［J］. Gastroenterology, 2006, 130(3):759-770.
［12］孙金山，江逊，仝海霞，张薇，兰莉，王宝西.BALB/c小鼠溃疡性结肠炎远段结肠Cajal间质细胞分布变化研究［J］. 实用儿科临床杂志, 2007, 22(12):925-927.
［13］Lee JI, Park H, Kamm MA, Talbot IC. Decreased density of interstitial cells of Cajal and neuronal cells in patients with slow-transit constipation and acquired megacolon［J］. J Gastroenterol Hepatol, 2005, 20(8):1292-1298.
［14］Kostin S. Zonula occludens-1 and connexin 43 expression in the failing human heart［J］. J Cell Mol Med, 2007, 11(4):892-895.
［15］Francis RJ, Lo CW. Primordial germ cell deficiency in the connexin 43 knockout mouse arises from apoptosis associated with abnormal p53 activation［J］. Development, 2006, 133(17):3451-3460.
［16］Ikeda Y, Fry C, Hayashi F, Stolz D, Griffiths D, Kanai A. Role of gap junctions in spontaneous activity of the rat bladder［J］. Am J Physiol Renal Physiol, 2007, 293(4):F1018-1025.
［17］Khanam T, Burnstock G. Changes in expression of P2X1 receptors and connexin 43 in the rat myometrium during pregnancy［J］. Fertil Steril, 2007, 88(4 Suppl):1174-1179.
［18］高红，张志波，王维林，黄英.先天性巨结肠Pax3和Cx43基因突变及表达［J］.世界华人消化杂志, 2004, 12(9)：2254-2256.
［19］刘远梅，胡月光，方勇，杨晓红.经肛门Ⅰ期根治巨结肠及应用解剖研究［J］.中国当代儿科杂志，2003，5（2）：135-136.
