慢传输便秘的临床研究及其结肠Cajal细胞变化规律的研究
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摘要
慢传输性便秘(slow transit constipation，STC)是较常见的一类功能性顽固性便秘，发病机制不清，保守治疗对STC效果有限，严重者最终只有手术切除全(次全)结肠。但创伤大，术后腹泻、便秘复发、粘连性肠梗阻依然困扰着外科医师。如何重新评价便秘的诊断与外科治疗，如何通过对病变结肠段的定位而采取选择性结肠段的切除，是当今便秘外科最重要的课题。近年来的研究证实Cajal间质细胞(interstitial cells ofCajal，ICC)是介于肠神经系统和平滑肌细胞之间的一类极其特殊的间质细胞，是胃肠道慢波的起搏细胞，对肠神经信号传递到平滑肌起重要的调控作用，探索ICC的病理变化可望成为STC发病机制研究的突破点。本课题采用结肠运输功能试验、盆腔四重造影、肛门直肠测压和全肠腔内测压顽固性便秘患者进行正确系统诊断和初步定位并进行选择性结肠段的切除手术研究。采用免疫组织化学方法和免疫荧光染色结合激光共聚焦显微镜技术分析观察STC结肠各段ICC分布、形态和数量变化。结果显示：
1．结肠运输试验是目前诊断慢传输型便秘的重要首选检查方法。盆腔四重造影检查正确诊断难以发现的STC伴发隐匿盆底疾病，是诊断慢传输型便秘必须必要的。不同类型的便秘存在不同的结肠、肛门直肠动力学改变和直肠感觉异常，把便秘分型后再进行肛门直肠测压可体现不同的发病机制，同时可针对不同类型便秘采取不同的治疗方案。全结肠测压对诊断STC的具体结肠段起着十分重要的意义。对手术切除肠管的选择起了指导意义。93％的患者认为手术效果良好．
2．STC患者全结肠ICC均显著减少，残存的ICC突起变短、变钝。以横结肠和直肠乙状结肠部ICC减少为著。暗示表明ICC数量减少和形态异常在STC的发病机制中扮演了重要的角色。回盲部可能是结肠慢波的起博点。HE染色及超微结构观察均未见到明显的与ICC相关的细胞变性、坏死和凋亡，暗示ICC的异常变化可能与细胞表型转化等其他机制有关。
Slow transit constipation (STC) is a colonic motor disorder, which is characterized by measurably delayed movement of materials through the colon. Although abnormalities in the neuronal networks of the colon have been demonstrated. in patients with STC, the aetiology of it remains unclear. The severity of its symptoms and the failure of the conservative therapy ultimately led to colectomy for some patients with STC.However,a number of patients experience postoperative side effects such as diarrhea, recurrence of constipation, adhesive ileus It is capital for STC how to re-evaluate surgical treatment and diagnose of STC,how to clear range of disorder for high elective colectomy. Interstitial cells of Cajal (ICC) have been shown to be the pacemaker cells of the intestine and have been implied in the pathogenesis of a number of gastrointestinal motility dysfunction including idiopathic slow transit constipation.It will be a major breakthrough in this field to search for on distribution of interstitial cells of Cajal in the colon of patients with STC. In this present study cases with constipation were examined by colonic transit test, pelvicography and colpocystodefecography, anorectal manometry, pancolonic manometry. according to the result, cases were classified and diagnosed for range of disorder and experienced high elective colectomy. Based on the routine microscope examination, the distribution and configuration of ICC were observed with immunohistochemistry. With an indirect immunofluorescence staining, ICC were examined with a laser scanning confocal microscope and the area occupied by ICC were calculated with an image analysis system. And the ultrastructure of ICC were observed by an electron microscope. The results were as following:
1.Colonic transit test is a preferred and signifiable examination techniques for STC. Pelvicography and colpocystodefecography, anorectal manometry can find hiding complaint of pelvic floor.It is needs and necessary for diagnoses of STC.By anorectal manometry,the results may provide diagnostic information. Different constipation have different results. Different results can represent different pathogenesis.So according to different pathogenesis and results,we used different surgical treatment. The pressure of colon between the normal and the constipational is different. The measurement of pancolonic manometry is useful for the slow transit constipation patient to have high elective colectomy.93 percent of the patients recovered well and have a normal frequency of defecation 6 months postoperatively. The surgical treatment is valuable for the slow transit constipation treatment.
2. The data suggest that ICC distribution is relatively uniform throughout the human colon and that decreased ICC volume is pan-colonic in slow transit constipation. The remaining ICC in the STC patients appeared blunted and shorter when compared with processes from ICC visualized in the controls. The myenteric plexus ICC is denser in the caecum colon. So we presume the caecum is the primary colonic pacemaker site. Our studies revealed decreased area of c-kit positice ICC in the STC colon, which may play an important role in the pathogenesis of STC. H-E staining displayed that most patients have no obvious abnormal presentation. Electron microscope showed that ICC were relatively sparsity. The Space between ICC and smooth muscle enlarged. Decreased or abnormal ICC found within the STC colon may not related to cell degeneration, apoptosis, or necrosis.
1．结肠运输试验是目前诊断慢传输型便秘的重要首选检查方法。盆腔四重造影检查正确诊断难以发现的STC伴发隐匿盆底疾病，是诊断慢传输型便秘必须必要的。不同类型的便秘存在不同的结肠、肛门直肠动力学改变和直肠感觉异常，把便秘分型后再进行肛门直肠测压可体现不同的发病机制，同时可针对不同类型便秘采取不同的治疗方案。全结肠测压对诊断STC的具体结肠段起着十分重要的意义。对手术切除肠管的选择起了指导意义。93％的患者认为手术效果良好．
2．STC患者全结肠ICC均显著减少，残存的ICC突起变短、变钝。以横结肠和直肠乙状结肠部ICC减少为著。暗示表明ICC数量减少和形态异常在STC的发病机制中扮演了重要的角色。回盲部可能是结肠慢波的起博点。HE染色及超微结构观察均未见到明显的与ICC相关的细胞变性、坏死和凋亡，暗示ICC的异常变化可能与细胞表型转化等其他机制有关。
Slow transit constipation (STC) is a colonic motor disorder, which is characterized by measurably delayed movement of materials through the colon. Although abnormalities in the neuronal networks of the colon have been demonstrated. in patients with STC, the aetiology of it remains unclear. The severity of its symptoms and the failure of the conservative therapy ultimately led to colectomy for some patients with STC.However,a number of patients experience postoperative side effects such as diarrhea, recurrence of constipation, adhesive ileus It is capital for STC how to re-evaluate surgical treatment and diagnose of STC,how to clear range of disorder for high elective colectomy. Interstitial cells of Cajal (ICC) have been shown to be the pacemaker cells of the intestine and have been implied in the pathogenesis of a number of gastrointestinal motility dysfunction including idiopathic slow transit constipation.It will be a major breakthrough in this field to search for on distribution of interstitial cells of Cajal in the colon of patients with STC. In this present study cases with constipation were examined by colonic transit test, pelvicography and colpocystodefecography, anorectal manometry, pancolonic manometry. according to the result, cases were classified and diagnosed for range of disorder and experienced high elective colectomy. Based on the routine microscope examination, the distribution and configuration of ICC were observed with immunohistochemistry. With an indirect immunofluorescence staining, ICC were examined with a laser scanning confocal microscope and the area occupied by ICC were calculated with an image analysis system. And the ultrastructure of ICC were observed by an electron microscope. The results were as following:
1.Colonic transit test is a preferred and signifiable examination techniques for STC. Pelvicography and colpocystodefecography, anorectal manometry can find hiding complaint of pelvic floor.It is needs and necessary for diagnoses of STC.By anorectal manometry,the results may provide diagnostic information. Different constipation have different results. Different results can represent different pathogenesis.So according to different pathogenesis and results,we used different surgical treatment. The pressure of colon between the normal and the constipational is different. The measurement of pancolonic manometry is useful for the slow transit constipation patient to have high elective colectomy.93 percent of the patients recovered well and have a normal frequency of defecation 6 months postoperatively. The surgical treatment is valuable for the slow transit constipation treatment.
2. The data suggest that ICC distribution is relatively uniform throughout the human colon and that decreased ICC volume is pan-colonic in slow transit constipation. The remaining ICC in the STC patients appeared blunted and shorter when compared with processes from ICC visualized in the controls. The myenteric plexus ICC is denser in the caecum colon. So we presume the caecum is the primary colonic pacemaker site. Our studies revealed decreased area of c-kit positice ICC in the STC colon, which may play an important role in the pathogenesis of STC. H-E staining displayed that most patients have no obvious abnormal presentation. Electron microscope showed that ICC were relatively sparsity. The Space between ICC and smooth muscle enlarged. Decreased or abnormal ICC found within the STC colon may not related to cell degeneration, apoptosis, or necrosis.
引文
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