Cajal间质细胞在先天性巨结肠和巨结肠同源病结肠中分布的观察
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摘要
目的:
通过免疫组化方法标记先天性巨结肠(Hirschsprung’s Disease,HD )和巨结肠同源病(Allied Hirschsprung’s Disease,AHD)肠壁内Cajal间质细胞(interstitial cells of cajal,ICCs),观察ICCs的分布状态,以探讨HD和AHD的发病机制
方法:
选经钡剂灌肠,直肠肛管测压,乙酰胆碱酯酶检测,以及病理组织学检查确证为HD和AHD的患者各20例,取吻合口远端直肠和近端结肠的全层肠壁作为实验组。另取16例正常结肠标本作为对照组。分别用鼠抗人c-kit单克隆抗体(CD117),常规SP法免疫组化染色,DAB显色,以PBS代替一抗染色作阴性对照,行甲苯胺蓝染色鉴别肥大细胞。光镜下观察ICCs的分布,用ImagePro-Plus图像分析系统检测ICCs的面积,对HD和AHD的远端和近端结肠肠壁内ICCs进行统计学分析。
结果:
对照组:ICCs主要分布在肌间神经丛周围和环纵肌层内,神经丛周围ICCs包绕分布,彼此之间紧密连接,肌层间可见连续分布的ICCs,与周围界限明显;肌层内ICCs位于肌间隔内,平行于肌细胞走形。
HD组远端肠管(即无神经节细胞区):神经丛周围和各肌层内ICCs明显减少甚至缺如,ICCs间无连接;近端肠管(有神经节细胞区):ICCs丰富,大量分布于环肌层内形成网络结构,肌间神经丛同样有大量ICCs分布;比较近远端肠壁内ICCs的分布差异有统计学意义(P<0.001)。
近端与对照组比较差异没有显著性(P>0.1),远端与对照组比较差异有统计学意义(P<0.001)。
AHD组:远端肠管:神经丛大小不一,ICCs分布差异大;主要分布于肌间神经丛周围和环肌层内。有的神经丛周围可见ICCs围绕,但有的周围则缺如,大多数神经丛区ICCs减少,环肌层内ICCs明显减少;近端肠管:ICCs丰富,但个别标本近远端肠壁内ICCs均有减少;比较AHD组近远端肠壁内ICCs分布差异有统计学意义(P<0.001)。近端与对照组比较差异没有显著性(P>0.1),远端与对照组比较差异有统计学意义(P<0.001)。
总体比较HD组、AHD组远端肠管及对照组中ICCs分布,其差异有显著性统计学意义(〈P0.001)。HD组与AHD远端肠管ICCs分布的差异有显著性统计学意义(P〈0.05)。对照组和近端肠管总体比较三组间无明显差异。
结论:
本研究证实HD、AHD病变肠管中除了神经节细胞的异常外,病变肠管中还缺少ICCs。ICCs的减少和分布异常必然导致结肠慢波节律和兴奋传导的异常,从而引起或加重HD和AHD的病情。ICCs在HD与AHD之间的分布不同可能与这两者之间的临床症状差异存在相关性;AHD组内ICCs的分布差异支持AHD患者临床症状的多样性。肠管中残存的ICCs可能与临床症状的轻重程度以及预后有一定关系。
Objective
The aim of this study was to examine the distrubution of Interstitial Cells of Cajal (ICCs) in the colon of patients with Hirschsprung’s Disease and with Allied Hirschsprung’s Disease,and to find out the role of ICCs in the pathogenesis of Hirschsprung’s disease (HD) and Allied Hirschsprung’s Disease (AHD) .
Method
20 patients with HD、20 with AHD and 16 controls were studied. ICCs were indentified with a monoclonal antibody to c-kit(CD117) by immunochistrychemistry method. The area occupied by ICCs was calculated with ImagePro-Plus analysis software. The result was ananlised by SPSS12.0 software.
Results
ICCs were abundant and locatied in the myenteric plexus(MP)、the circle muscle(CM) and longest muscle(LM).In HD aganglionic colone , ICCs were very scarce, but in the proximal part ,ICCs were abuduant.The siginificiant diference was between the proximal part and the distal part (P<0.001).But the difference between the proximal colone of HD and control was not obviously (P >0.1). In AHD bowel ,ICCs cells were weaker and mainly locatied in MP in the distal clone .The distribution of ICCs in AHD distal colon was diference(P<0.001). In the distal colon,there were significiant diference in the three groups;In the proxima part ,the diference was no clear(P >0.1)
Conclusion
This study reveals the relation between the abnormal distribution of ICCs and the pathogenesis of HD、AHD. It is suspected the lack or reduction of ICCs would be responsible for the gastrointestinal motility dysfunction, which is an importent factor in the pathogenesis of AHD and HD. The difference of ICC may be relatied with their different signs and symptoms.
通过免疫组化方法标记先天性巨结肠(Hirschsprung’s Disease,HD )和巨结肠同源病(Allied Hirschsprung’s Disease,AHD)肠壁内Cajal间质细胞(interstitial cells of cajal,ICCs),观察ICCs的分布状态,以探讨HD和AHD的发病机制
方法:
选经钡剂灌肠,直肠肛管测压,乙酰胆碱酯酶检测,以及病理组织学检查确证为HD和AHD的患者各20例,取吻合口远端直肠和近端结肠的全层肠壁作为实验组。另取16例正常结肠标本作为对照组。分别用鼠抗人c-kit单克隆抗体(CD117),常规SP法免疫组化染色,DAB显色,以PBS代替一抗染色作阴性对照,行甲苯胺蓝染色鉴别肥大细胞。光镜下观察ICCs的分布,用ImagePro-Plus图像分析系统检测ICCs的面积,对HD和AHD的远端和近端结肠肠壁内ICCs进行统计学分析。
结果:
对照组:ICCs主要分布在肌间神经丛周围和环纵肌层内,神经丛周围ICCs包绕分布,彼此之间紧密连接,肌层间可见连续分布的ICCs,与周围界限明显;肌层内ICCs位于肌间隔内,平行于肌细胞走形。
HD组远端肠管(即无神经节细胞区):神经丛周围和各肌层内ICCs明显减少甚至缺如,ICCs间无连接;近端肠管(有神经节细胞区):ICCs丰富,大量分布于环肌层内形成网络结构,肌间神经丛同样有大量ICCs分布;比较近远端肠壁内ICCs的分布差异有统计学意义(P<0.001)。
近端与对照组比较差异没有显著性(P>0.1),远端与对照组比较差异有统计学意义(P<0.001)。
AHD组:远端肠管:神经丛大小不一,ICCs分布差异大;主要分布于肌间神经丛周围和环肌层内。有的神经丛周围可见ICCs围绕,但有的周围则缺如,大多数神经丛区ICCs减少,环肌层内ICCs明显减少;近端肠管:ICCs丰富,但个别标本近远端肠壁内ICCs均有减少;比较AHD组近远端肠壁内ICCs分布差异有统计学意义(P<0.001)。近端与对照组比较差异没有显著性(P>0.1),远端与对照组比较差异有统计学意义(P<0.001)。
总体比较HD组、AHD组远端肠管及对照组中ICCs分布,其差异有显著性统计学意义(〈P0.001)。HD组与AHD远端肠管ICCs分布的差异有显著性统计学意义(P〈0.05)。对照组和近端肠管总体比较三组间无明显差异。
结论:
本研究证实HD、AHD病变肠管中除了神经节细胞的异常外,病变肠管中还缺少ICCs。ICCs的减少和分布异常必然导致结肠慢波节律和兴奋传导的异常,从而引起或加重HD和AHD的病情。ICCs在HD与AHD之间的分布不同可能与这两者之间的临床症状差异存在相关性;AHD组内ICCs的分布差异支持AHD患者临床症状的多样性。肠管中残存的ICCs可能与临床症状的轻重程度以及预后有一定关系。
Objective
The aim of this study was to examine the distrubution of Interstitial Cells of Cajal (ICCs) in the colon of patients with Hirschsprung’s Disease and with Allied Hirschsprung’s Disease,and to find out the role of ICCs in the pathogenesis of Hirschsprung’s disease (HD) and Allied Hirschsprung’s Disease (AHD) .
Method
20 patients with HD、20 with AHD and 16 controls were studied. ICCs were indentified with a monoclonal antibody to c-kit(CD117) by immunochistrychemistry method. The area occupied by ICCs was calculated with ImagePro-Plus analysis software. The result was ananlised by SPSS12.0 software.
Results
ICCs were abundant and locatied in the myenteric plexus(MP)、the circle muscle(CM) and longest muscle(LM).In HD aganglionic colone , ICCs were very scarce, but in the proximal part ,ICCs were abuduant.The siginificiant diference was between the proximal part and the distal part (P<0.001).But the difference between the proximal colone of HD and control was not obviously (P >0.1). In AHD bowel ,ICCs cells were weaker and mainly locatied in MP in the distal clone .The distribution of ICCs in AHD distal colon was diference(P<0.001). In the distal colon,there were significiant diference in the three groups;In the proxima part ,the diference was no clear(P >0.1)
Conclusion
This study reveals the relation between the abnormal distribution of ICCs and the pathogenesis of HD、AHD. It is suspected the lack or reduction of ICCs would be responsible for the gastrointestinal motility dysfunction, which is an importent factor in the pathogenesis of AHD and HD. The difference of ICC may be relatied with their different signs and symptoms.
引文
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9. Sanders K.M, Development and plasticity of interstitial cells of Cajal. Neurogastroenterol Motil, 1999. 11(5): p. 311-338.
10. Ward S.M, Ordog T, Koh SD,et al . Sanders K.M. Physiology and pathophysiology of the interstitial cell of Cajal: from bench to bedside. I. Functional development and plasticity of interstitial cells of Cajal networks. Am J Physiol Gastrointest Liver Physiol, 2001. 281(3): p. G602-11.
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13.于彬,周德山,双重染色显示Cajal细胞和NOS神经在胎儿小肠肌间神经丛的分布.第三军医大学学报, 2004. 26(18).
14.龙庆林,房殿春胃肠道Cajal细胞的功能及相关疾病.世界华人消化杂志, 2002. 10(3): p. 352-355.
15. Wang XY, Sanders KM., Ward SM. Intimate relationship between interstitial cells of cajal and enteric nerves in the guinea-pig small intestine. Cell Tissue Res, 1999. 295(2): p. 247-56.
16. Lecoin L, Gabella G., Douarin N. Le . Origin of the c-kit-positive interstitial cells in the avian bowel. Development, 1996. 122(3): p. 725-33.
17. Vanderwinden J.M. Role of Interstitial Cells of Cajal and their relationship with the enteric nervous system. Eur J Morphol, 1999. 37(4-5): p. 250-6.
18. Hagger R, Gharaie S, Finlayson C,et al. Regional and transmural density ofinterstitial cells of Cajal in human colon and rectum. Am J Physiol, 1998. 275(6 Pt 1): p. G1309-16.
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