Cajal间质细胞与慢传输型便秘之间关系研究进展

0引言 Cajal间质细胞（ICC）是分布于胃肠道平滑肌和神经细胞之间的一类特殊细胞,它具有产生慢波,传导电兴奋和参与神经递质调节的重要功能。     

Cajal间质细胞与慢传输型便秘

慢性便秘中近一半属于慢传输型便秘,其病因复杂,机制尚不明了。研究证实Cajal间质细胞是胃肠道的起搏细胞,产生慢波和传导电兴奋,参与神经递质的调节。近期研究表明慢性便秘患者结肠组织中Cajal间质细胞数量减少,形态及其网状结构改变,这在慢传输型便秘发病中具有重要的病理生理学意义。     

Cajal间质细胞与慢传输型便秘研究的现状与趋势

Cajal间质细胞(ICC)是分布在胃肠道神经细胞与平滑肌之间的一种特殊细胞,具有起搏及协调胃肠道运动的功能。研究发现慢传输型便秘(STC)患者结肠组织中Cajal间质细胞数量减少,形态及其网状结构改变,因此ICC的异常可能是STC的重要发病机制。预防或干预ICC的病变,积极改善ICC的功能,协调肠道运动可能是潜在治疗STC的方向。     

大鼠胃肠道不同部位Cajal间质细胞与慢传输型便秘的关系

目的观察慢传输型便秘(slow transit constipation,STC)大鼠模型胃肠道Cajal间质细胞(interstitial cell of cajal,ICC)的分布特点与含量改变,全面评估ICC在STC发病机制中的作用。方法 24只健康Wistar大鼠随机分成便秘组和对照组,分别饲喂含复方苯乙哌啶的混悬液和生理盐水,每5 d记录1次大鼠大便粒数、大便干质量及大鼠体质量。饲养90 d后停药1周,测定胃肠道传输功能并通过免疫组化的方法测定ICC的特异性标志物c-kit+细胞在胃窦、小肠、结肠的分布情况与含量变化。结果便秘组日均粪便粒数少于对照组(P<0.01),平均每粒粪便质量大于对照组(P<0.05);便秘组首粒黑便排出时间长于对照组(P<0.05);与对照组比较,便秘组胃窦部位c-kit+细胞数量无明显变化(P>0.05)。而c-kit+细胞在便秘组大鼠小肠、结肠的数目均少于对照组(P<0.05)。结论在STC模型中,胃窦ICC变化不明显,小肠ICC数量有减少趋势,可能对STC有一定影响,结肠部位ICC数量明显减少,可能是慢传输型便秘大鼠的主要病理生理机制。     

肠神经系统与慢传输型便秘

慢传输型便秘(STC)病因未明,多因素与其发病相关.肠神经系统(ENS)可独立调节肠道功能,其在慢传输型便秘中的改变具有重要意义.此文就此予以阐述,为STC临床治疗提供依据.     

慢传输型便秘动物模型研究进展

慢传输型便秘（slowtransitconstipationSTC）是一种以结肠通过时间延长和结肠动力下降为特征的顽固性便秘，是功能性便秘中常见的类型。随着人们饮食结构、生活习惯以及精神心理等因素的影响，其发病率呈逐年上升趋势。美国一项回顾性研究发现STC占慢性便秘患者的42．0%，是慢性便秘常见的病理类型。国内流行病学调查显示，     

慢传输型便秘发病机理研究进展

慢传输型便秘(slow transit constipation，STC)主要表现为结肠传输减慢，病因不明，治疗困难。文章对近年来sTC发病机理方面的研究进展，肠神经系统神经递质如NO、VIP、阿片肽；胃肠激素如SS、CCK等的变化及Cajal间质细胞、肠神经元病变、精神心理等因素与STC的关系作一综述。     

慢传输型便秘发病机制的研究

慢传输型便秘(STC)的发病机制主要与肠神经系统(ENS)、Cajal间质细胞(ICC)、平滑肌、神经递质等有关。研究发现STC结肠组织中ENS出现退行性变化,肌间神经丛空泡变性,ICC数量减少,形态改变,平滑肌退行性变,多种神经递质发生改变。本文就STC发病机制的研究作一综述。     

慢传输型便秘发病机制的研究进展

慢传输型便秘(STC)病因未明,多种因素如肠神经系统、肠神经递质、胃肠激素、Cajal间质细胞等与其发病相关。此文就此予以阐述,为STC临床治疗提供依据。     

慢传输型便秘发病机制的研究

慢传输型便秘（STC）是指由于结肠动力障碍,使内容物滞留在结肠及结肠运输缓慢所致的便秘。STC的病因复杂,确切的发病机制尚不完全清楚,症状顽固,治疗困难,主要与精神心理因素、肠神经系统（ENS）病理变化、Cajal间质细胞（ICC）的病理改变、平滑肌及肠神经递质变化等因素有关。此文就STC发病机制方面的研究进展作一综述,以期对临床治疗提供指导。     

Enteric nerves and interstitial cells of Cajal are altered in patients with slow-transit constipation and megacolon

BACKGROUND & AIMS: A variety of gastrointestinal motility disorders have been attributed to alterations of interstitial cells of Cajal and malformations of the enteric nervous system. This study evaluates both the distribution of interstitial cells of Cajal and the pathohistology of the enteric nervous system in 2 severe human colorectal motility disorders. METHODS: Colonic specimens obtained from patients with slow-transit constipation (n = 11), patients with megacolon (n = 6), and a control group (n = 13, nonobstructing neoplasia) were stained with antibodies against c-kit (marker for interstitial cells of Cajal) and protein gene product 9.5 (neuronal marker). The morphometric analysis of interstitial cells of Cajal included the separate registration of the number and process length within the different regions of the muscularis propria. The structural architecture of the enteric nervous system was assessed on microdissected whole-mount preparations. RESULTS: In patients with slow-transit constipation, the number of interstitial cells of Cajal was significantly decreased in all layers except the outer longitudinal muscle layer. The myenteric plexus showed a reduced ganglionic density and size (moderate hypoganglionosis) compared with the control group. Patients with megacolon were characterized by a substantial decrease in both the number and the process length of interstitial cells of Cajal. The myenteric plexus exhibited either complete aganglionosis or severe hypoganglionosis. CONCLUSIONS: The enteric nervous system and interstitial cells of Cajal are altered concomitantly in slow-transit constipation and megacolon and may play a crucial role in the pathophysiology of colorectal motility disorders.     

Decreased density of interstitial cells of Cajal and neuronal cells in patients with slow-transit constipation and acquired megacolon

BACKGROUND: The pathophysiology of constipation is not clearly identified as yet, and the interstital cells of Cajal (ICC), known to generate the slow wave activity and to be involved in intestinal neurotransmission and the enteric nervous system (ENS), are suspected to play an important role. The aims of the present study were to assess the distribution of ICC and neuronal cells of ENS in patients with slow-transit constipation and acquired megacolon. METHODS: Sigmoid colon specimens were obtained from patients who underwent colectomy due to slow-transit constipation (n = 10), acquired megacolon (n = 9) and non-obstructive colon cancer (n = 10) as a control group. The ICC were visualized by c-Kit immunohistochemistry and neuronal cells of the ENS were demonstrated by protein gene product (PGP) 9.5. Density of cells stained by c-Kit and PGP 9.5 was calculated as percent area (area stained/area of X-Y plane) x 100, when images were collected at a magnification of x40 objective, with maximum area examined in the horizontal X-Y plane of 400 microm x 400 microm using an image analyzer. RESULTS: The densities of ICC and PGP 9.5 reactive neuronal structures were significantly decreased in all layers of sigmoid colon specimens in patients with slow-transit constipation and acquired megacolon, compared with that of the control group. However, there was no statistically significant difference in either the density of ICC or that of neuronal structures between the patients with slow-transit constipation and acquired megacolon. CONCLUSIONS: Slow-transit constipation and acquired megacolon were associated with alteration of ICC and neuronal cells of ENS in the sigmoid colon.     

Decreased interstitial cell of cajal volume in patients with slow-transit constipation

BACKGROUND & AIMS: The cause of slow-transit constipation is incompletely understood. Recent observations suggest a central role for interstitial cells of Cajal in the control of intestinal motility. The aim of this study was to determine the volume of interstitial cells of Cajal in the normal sigmoid colon and in the sigmoid colon from patients with slow transit constipation. METHODS: Sigmoid colonic samples were stained with antibodies to protein gene product 9.5, c-Kit, and alpha-smooth muscle actin. Three-dimensional reconstruction of regions of interest was performed using consecutive images collected on a laser scanning confocal microscope and ANALYZE software. RESULTS: Volume of interstitial cells of Cajal was significantly decreased in all layers of sigmoid colonic specimens from patients with slow-transit constipation compared with normal controls. Neuronal structures within the colonic circular smooth muscle layer were also decreased. CONCLUSIONS: A decrease in the volume of interstitial cells of Cajal may play an important role in the pathophysiology of slow-transit constipation.     

Biliary dyskinesia in idiopathic slow-transit constipation

BACKGROUND: Idiopathic slow-transit constipation may be a pangastrointestinal motility disorder. We have screened patients referred to surgery for constipation for the presence of biliary dyskinesia. METHOD: Patients had cholecystokinin-augmented trimethyl-3-bromo iminodiacetic acid scans to measure gallbladder ejection fraction. RESULTS: There is a significant difference in gallbladder ejection fraction between patients with idiopathic slow-transit constipation (median value, 28.5) compared with patients with other causes of constipation (median value, 71; Mann-Whitney,P =0.0025). CONCLUSION: Idiopathic slow-transit constipation may be a pangastrointestinal motility disorder.Read at the meeting of the Association of Coloproctology, London, United Kingdom, June 9 to 11, 1994, and the meeting of the British Society of Gastroenterology, Edinburgh, Scotland, September 21 to 23, 1994.     

Ambulatory 24-hour colonic manometry in slow-transit constipation

BACKGROUND: The colonic neuromuscular dysfunction in patients with constipation and the role of colonic manometry is incompletely understood. AIM: To study prolonged colonic motility and assess its clinical significance. METHODS: Twenty-four-hour ambulatory colonic manometry was performed in 21 patients with slow-transit constipation and 20 healthy controls by placing a 6-sensor solid-state probe up to the hepatic flexure. Quantitative and qualitative manometric analysis was performed in 8-h epochs. Patients were followed up for 1 yr. RESULTS: Constipated patients showed fewer pressure waves and lower area under the curve (p < 0.05) than controls during daytime, but not at night. Colonic motility induced by waking or meal was decreased (p < 0.05) in patients. High-amplitude propagating contractions (HAPCs) occurred in 43% of patients compared to 100% of controls and with lower incidence (1.7 vs 10.1, p < 0.001) and propagation velocity (p < 0.04). Manometric features suggestive of colonic neuropathy were seen in 10, myopathy in 5, and normal profiles in 4 patients. Seven patients with colonic neuropathy underwent colectomy with improvement. The rest were managed conservatively with 50% improvement at 1 yr. CONCLUSIONS: Patients with slow-transit constipation exhibited either normal or decreased pressure activity with manometric features suggestive of colonic neuropathy or myopathy as evidenced by absent HAPC or attenuated colonic responses to meals and waking. In refractory patients, colonic manometry may be useful in characterizing the underlying pathophysiology and in guiding therapy.     

Biofeedback avoids surgery in patients with slow-transit constipation

Biofeedback is established treatment for intractable constipation in patients with an element of pelvic floor dysfunction. In those with intractable slow-transit constipation and normal pelvic floor function, colectomy is usually recommended. We report four patients with isolated slow-transit constipation who benefited from biofeedback and avoided surgery. All four patients were extensively investigated for pelvic floor dysfunction before undergoing a standard biofeedback course of four outpatient sessions. All improved in terms of bowel frequency, laxative use, bloating, straining, and lifestyle. Improvement has been maintained for a median of nine (range, 5–12) months without the requirement for further treatment. Biofeedback represents a safe and inexpensive treatment for these patients and may avoid surgery in a significant proportion.     

Pelvic motility and response to intraluminal bisacodyl in slow-transit constipation

The resting motility of the pelvic colon was studied in 28 patients with constipation and compared with control subjects and patients with diarrhea. Colonic activity in patients who had been shown to have slow colonic transit was not significantly different from controls. In contrast, activity in patients who complained of constipation but who were found to have normal colonic transit time was increased (P<0.02). The response of the pelvic colon to the introduction of a surface-acting laxative was studied in 18 patients with slow-transit constipation. Eleven patients developed progressive peristaltic waves, while in 7 there was no response. It is possible that the relative inactivity of the colon in the latter group is due to a disorder of the myenteric plexus. If so, the bisacodyl stimulation test may distinguish patients with an abnormal myenteric plexus from those in whom it is normal.Preston was supported by a grant from the St. Mark's Research Foundation.