刺激性泻剂对大鼠结肠肌间神经丛超微结构的影响

目的本实验主要研究刺激性泻剂对大鼠结肠肌间神经丛超微结构的影响及其在慢性便秘发生、发展过程中的作用机制。方法通过建立“泻剂结肠”的动物模型,应用电镜技术对正常大鼠及模型大鼠结肠肠壁肌间神经丛超微结构进行观察及对照研究。结果与正常对照组相比,“泻剂结肠”大鼠肠壁肌间神经丛超微结构有明显的病理损害,表现为结肠肌间神经丛可见神经元细胞线粒体轻度肿胀,神经纤维轴突内线粒体肿胀破裂,“嵴”状结构不完整,神经束轴突及树突扩张,电子密度不均匀,部分明显扩张形成空泡。结论长期应用刺激性泻剂可损害结肠肌间神经丛,其超微结构的改变可能是慢性便秘进一步发展和加重的病理基础之一。     

腹泻型肠易激综合征模型大鼠肠道Cajal间质细胞的变化及意义

目的：通过检测肠壁组织中酪氨酸激酶受体C-kit蛋白（C-kit）的表达及分布，观察Cajal间质细胞在腹泻型肠易激综合征模型大鼠小肠、回盲部及结肠中的变化，并初步探讨其变化在肠易激综合征中的意义。方法：通过对新生大鼠结直肠扩张（colorectal distension，CRD）制备肠易激综合征模型，40 d后观察大便性状；通过腹壁回撤反应(abdominal withdrawal reflex，AWR)评分评估内脏敏感性；小肠、回盲部及结肠组织常规HE染色，光镜下观察病理学变化；免疫组化检测肠壁组织中C-kit的表达及分布。结果：实验组大鼠大便Bristol评分明显升高；在相同压力的直肠刺激下AWR评分明显高于对照组；小肠、回盲部及结肠组织的C-kit表达显著增强。结论：新生大鼠结直肠扩张可以制备肠道分泌、运动和内脏敏感性均增强的肠易激综合征模型；Cajal间质细胞可能在腹泻型肠易激综合征发病中有重要的意义。     

干细胞与胃肠动力障碍性疾病的关系研究进展

胃肠动力障碍性疾病是一种常见的消化道疾病。干细胞的研究可能为胃肠动力障碍性疾病的治疗提供新的方法和思路。目前国内外关于干细胞与胃肠动力关系的研究甚少 ,主要包括以下方面。1　Cajal间质细胞与胃肠动力障碍性疾Cajal间质细胞 (ICC)在胃肠平滑肌运动中起着重要的作用 ,它是胃肠运动的起搏者和肠运动神经与肌肉间的信息传递者。人类多种胃肠动力障碍性疾病与ICC的减少和缺失有关 ,如贲门失弛缓症就是由于ICC的缺失造成食管下段肌层持续收缩所致 ,此外还包括 :斑点病的先天性巨结肠 ,Cha gasic巨结肠 ,获得性巨结肠 ,慢性便秘 ,…     

全层铺片技术显示胃肠道不同部位Cajal间质细胞

正Cajal间质细胞(interstitial cells of Cajal,ICC),是西班牙神经解剖学家Santiago Ramony Cajal于1893年首次在胃肠道中发现的一类特殊间质细胞,与胃肠道平滑肌和神经纤维末梢在解剖学上有紧密联系,具有独立功能,既是胃肠起搏细胞,又具有传导神经递质的作用~[1]。ICC广泛存在于哺乳动物的整个消化道管壁内,按分布区域可大致分为:分布于胃、小肠和结肠内的环肌与纵行肌之间的肌间神经丛ICC;位于黏膜下环肌层表面的ICC;位于小肠深肌丛区域的ICC;广泛散布于环肌和纵肌肌束内的ICC~[2]。目前消化道全层铺片技术由于能够直观、全面地显示ICC的分布、形态以及形成的细胞网络,而成为研究胃肠神经系统的重要方法之一,但文献中却鲜少提及此方法的详细操作过程。已知ICC特异性表达由原癌基因c-kit编码的受体酪氨酸激酶     

Cajal间质细胞与糖尿病胃轻瘫

Cajal间质细胞(ICC)是胃肠慢波的起搏细胞,它参与神经肌肉信号的转导。ICC对慢波的产生、维持及胃肠动力功能起关键作用。糖尿病患者由于血糖控制不良,可引起胃肠功能紊乱,胃排空延迟,胃电起搏活动损伤,慢波节律失调。当糖尿病胃轻瘫时,ICC数目明显减少,甚至缺失,ICC网络结构破坏,甚至重建。     

小型猪胃肠道Cajal间质细胞超微结构的研究

目的明确小型猪胃肠道Cajal间质细胞(interstitialcellsofCajal,ICC)超微结构特点。方法麻醉后取小型猪胃肠组织小进行透射电镜观察。结果小型猪胃肠道壁内神经及Cajal间质细胞的突起相互连接形成网络,分布均匀。Cajal间质细胞的主要结构特点为:胞核清晰,完整的基膜,丰富的沿细胞膜分布的小空泡,细胞质内细胞器丰富,以线粒体最显著。以及内质网和发育良好的高尔基氏器,核糖体丰富,异染色质较多,沿核膜分布,其胞质突起围绕神经束形成不完整的“鞘”样结构。Cajal间质细胞之间、与神经元细胞、肌细胞之间形成很多的缝隙连接。结论Cajal间质细胞具有独特的超微结构特点,易于识别,且其超微结构特点与其功能相适应运动功能     

肠道间质细胞与肠道疾病

肠道间质细胞 (interstitalcellofCajal,ICC)是一类既不同于典型的平滑肌细胞 ,也不同于雪旺氏细胞的胃肠道的间质细胞 ,该细胞是 1893年西班牙神经解剖学家SantiagoRamonCajal首先对此类细胞作了详细的描述。后人称之为Cajal(卡哈尔 )细胞。多年来一直未引起人们的重视 ,近年来随着研究的不断深入 ,对其来源及功能有了进一步的认识 ,并发现此细胞与许多胃肠道疾病及肿瘤的发生有关。一、ICC的形态和分布在肠道的肠壁 ,有一种间质细胞穿插在平滑肌组织内 ,包绕Auerbush神经丛形成细胞网络 ,这种细胞叫ICC。近 2 0年引起科学家的重视。…     

人胚胎结肠肠神经系统发育的观察

目的　研究人胚胎结肠肠神经系统的发育过程 ,为进一步研究先天性巨结肠的发病机制提供参考。　方法　采用一抗为蛋白基因产物 (protein gene product9.5 ,PGP9.5 )和 S- 10 0蛋白抗体的免疫组织化学 PAP法 ,显示结肠肠神经系统中的神经元和神经胶质。　结果　人胚胎结肠肠神经系统发育有明显的阶段性。在胚胎发育早期 (胎龄 2～ 3月 ) ,肠管壁发育差 ,以后出现菲薄的平滑肌层和低平的肠粘膜 ,此期偶在原始肌间神经丛位置见S- 10 0蛋白免疫反应性神经 ;至发育中期 (胎龄 4～ 5月 ) ,肠壁分化出 4层结构 ,出现相当发达的绒毛 ,肌间神经丛中细胞明显增多 ,呈弥散分布于整个肌层间并逐渐迁移到粘膜下层和粘膜层 ,由初级和次级突起构成复杂的神经网络 ;至晚期 (6～ 9月 ) ,肠壁各层均增厚 ,肌间神经丛成簇分布 ,神经纤维构成的网络出现更为细小的 3级突起 ,粘膜下神经丛分化形成浅丛和深丛。　结论　结肠神经系的发育具有明显的阶段性。发育早期神经开始在肠壁肌间丛位置出现 ,发育中期神经成分在肠壁各层中出现并发育增生 ,晚期肠壁各层神经已分化和成熟 ,而在不同的发育阶段 ,原始病因可导致临床表现不一的先天性巨结肠症     

阻断C-KIT导致小鼠小肠基本电节律紊乱及Cajal间质细胞缺失

目的观察小鼠小肠在体基本电节律、Cajal间质细胞的分布及阻断C-K IT对其的影响。方法新生的Balb/c小鼠,腹腔内隔天注射C-K IT抗体(ACK2)100μg,共5次,对照组注射生理盐水。于小鼠出生后第10天测定小肠在体基本电节律活动。用免疫组化方法观察小肠Cajal间质细胞的分布。结果对照组小鼠的小肠在体基本电节律活动表现为近似正弦波形,ACK2处理组表现无规律。ACK2处理组小肠基本电节律的频率及幅度为(3.515±1.033)次/m in和(0.045±0.016)mV,均显著低于对照组的(13.997±0.976)次/m in和(0.086±0.018)mV(P<0.01)。对照组Cajal间质细胞主要分布于肌间神经丛区(ICC-MY)及深肌层丛区(ICC-DMP),而ACK2处理组未能明显观察到其分布。结论阻断C-K IT可导致小鼠小肠基本电节律紊乱及Cajal间质细胞缺失。     

卡巴胆碱对缺血/再灌注损伤肠道Cajal间质细胞的影响

目的： 观察缺血/再灌注损伤肠道Cajal间质细胞、炎症因子、氧自由基变化以及拟胆碱药卡巴胆碱对上述指标的影响。方法: 成年雄性SD大鼠, 随机分为手术对照（S）组、肠缺血再灌注（I/R）组和I/R+卡巴胆碱(I/R+CAR)组。 制备肠I/R模型,于夹闭后2.5 h处死动物, 取肠袋组织测定TNF-α含量、SOD活性和MDA含量;另取肠组织制作病理切片、进行Cajal间质细胞免疫组化染色。结果: I/R组肠组织中Cajal间质细胞阳性表达量比S组显著降低（P<0.01）, I/R+CAR组Cajal间质细胞阳性表达量显著高于I/R组(P<0.01）。I/R组MDA和TNF-α含量较S组显著升高(P<0.01)、SOD活性显著降低(P<0.01)。I/R+CAR组MDA和TNF-α含量与I/R组比较明显减少(P<0.01),SOD活性有所回升(P<0.05)。结论: 肠缺血/再灌注损伤时炎症因子及氧自由基增加,导致Cajal间质细胞损伤;卡巴胆碱可通过减少炎症因子释放及氧自由基损伤,减轻Cajal间质细胞的损伤。     

Unusual type of colonic neuromuscular disorder with extensive vacuolization

Various pathological abnormalities of smooth muscle and innervation result in clinical syndromes with disordered motility of the small intestine and colon. Although these abnormalities have been extensively reported clinically, their pathologic changes and pathophysiologic mechanisms have not been well elucidated. We report a case of visceral neuropathy with secondary muscle changes in a 7-yr-old ventilator dependent, mentally retarded child who presented with a history of chronic constipation and symptoms of intestinal obstruction. The muscle layer of the colectomy specimen showed extensive infiltration of vacuolated cells that were positive for S-100 and synaptophysin but negative for glial fibrillary acidic protein (GFAP) and neural filament protein (NFP). Calretinin positivity was preserved in submucosal ganglion cells but was absent in vacuolated nerve branches. Masson's trichrome stain showed evidence of fibrosis, indicative of muscle damage. There was a reduced number of intestinal cells of Cajal in the muscularis propria, as indicated by CD117 (c-kit) immunostaining. This disorder is most likely a sporadic visceral neuropathy, secondarily affecting muscular function, that causes colonic pseudo-obstruction.     

Enterisches Nervensystem und interstitielle Cajal-Zellen

Intestinal innervation disorders are part of the broad etiological spectrum of chronic constipation and need to be specifically addressed in differential diagnosis. The enteric nervous system constitutes the largest peripheral nervous system of its own ("brain in the gut"), and is involved in the mediation of intestinal motility. Morphologically different nerve cell types aggregate into intramural plexus layers and release a multitude of neurotransmitters. Malformations or lesions of the enteric nervous system may lead to a severely prolonged intestinal transit time resulting in chronic constipation resistant to conservative treatment. In contrast to the early manifestation of aganglionosis, non-aganglionic or acquired alterations to the intramural nerve plexus often remain unrecognised up to adulthood. Histopathological diagnosis is carried out by enzyme or immunohistochemical staining, either on sections or whole mount preparations, allowing an optimal visualization of the nerve plexus architecture. To diagnose hypoganglionosis, enteric ganglionitis or alterations in interstitial cells of Cajal, full-thickness biopsies are required. Interstitial cells of Cajal contribute significantly to the mediation of intestinal motility by generating "slow wave" activity. In adult patients with slow-transit constipation and megacolon, the intramuscular networks of the interstitial cells of Cajal show a significantly reduced density.     

Is pseudomelanosis coli a marker of colonic neuropathy in severely constipated patients?

AIMS: To study relationships between the number of pseudomelanosis coli cells and that of colonic enteric neurons and interstitial cells of Cajal, which are significantly reduced compared with controls in severely constipated patients. Pseudomelanosis coli is frequent in patients using anthraquinone laxatives. It is not known whether the prolonged use of these compounds damages the enteric nervous system in constipated patients. PATIENTS AND METHODS: The relationship between the number of pseudomelanosis coli cells and that of colonic enteric neurons (as well as that of apoptotic enteric neurons) and of interstitial cells of Cajal was assessed by histological and immunohistochemical methods in 16 patients with chronic use of anthraquinone laxatives undergoing surgery for severe constipation unresponsive to medical treatment. No relationship was found between the number of pseudomelanosis coli cells and that of enteric neurons (and that of the apoptotic ones), nor of interstitial cells of Cajal, in either the submucosal or the myenteric plexus. CONCLUSION: The use of anthraquinone laxatives, leading to the appearance of pseudomelanosis coli, is probably not related to the abnormalities of the enteric nervous system found in severely constipated patients.     

Interstitial cells of Cajal, enteric nerves, and glial cells in colonic diverticular disease

BACKGROUND: Colonic diverticular disease (diverticulosis) is a common disorder in Western countries. Although its pathogenesis is probably multifactorial, motor abnormalities of the large bowel are thought to play an important role. However, little is known about the basic mechanism that may underlie abnormal colon motility in diverticulosis. AIMS: To investigate the interstitial cells of Cajal (the gut pacemaker cells), together with myenteric and submucosal ganglion and glial cells, in patients with diverticulosis. PATIENTS: Full thickness colonic samples were obtained from 39 patients undergoing surgery for diverticulosis. Specimens from tumour free areas of the colon in 10 age matched subjects undergoing surgery for colorectal cancer served as controls. METHODS: Interstitial cells of Cajal were assessed using anti-Kit antibodies; submucosal and myenteric plexus neurones and glial cells were assessed by means of anti-PGP 9.5 and anti-S-100 monoclonal antibodies, respectively. RESULTS: Patients with diverticulosis had normal numbers of myenteric and submucosal plexus neurones compared with controls (p = 0.103 and p = 0.516, respectively). All subtypes of interstitial cells of Cajal were significantly (p = 0.0003) reduced compared with controls, as were glial cells (p = 0.0041). CONCLUSIONS: Interstitial cells of Cajal and glial cells are decreased in colonic diverticular disease, whereas enteric neurones appear to be normally represented. This finding might explain some of the large bowel motor abnormalities reported to occur in this condition.     

Morphologisches Bild der aplastischen und atrophischen Desmose des Darms

In addition to the enteric nervous system, the interstitial cells of Cajal and the smooth musculature, the collagenous fibre network of the muscularis propria plays a major role in the coordination of peristalsis. Partial or complete absence of this network in patients with chronic constipation has been described as 'desmosis'. Two major subtypes of desmosis can be distinguished: in the rare congenital (primary) aplastic desmosis of childhood, the collagenous fibre network is not formed. This is characteristic of microcolon megacystis syndrome and is associated with aperistalsis. The more common atrophic (secondary) desmosis of adulthood is typically incomplete and associated with a hypoperistaltic syndrome. Neither the etiology nor the pathogenesis of desmosis are currently understood. Atrophic desmosis may occur after previous inflammatory episodes. Further extensive studies are needed to better understand the pathogenesis, etiology and functional implications of this disease.     

The histology at various stages of acute rejection in concordant xenogeneic heart transplantation. A sequential study in rodents.

In an attempt to describe early morphologic changes in heterotopic xenogeneic heart transplantation a sequential study was performed in a hamster-to-rat model. Mild morphologic changes observed after four to six h were characterized by slight interstitial edema and focal myocyte damage with fragmentation and loss of myofibrillar elements. No lymphocytic infiltration appeared. Moderate morphologic changes observed after 12-24 h were characterized by moderate interstitial edema, and the appearance of mild hemorrhage and scattered extravasated neutrophilic granulocytes. The myocardium had more widespread areas with myocyte damage, sometimes with small foci of necrotic cells and adjacent neutrophilic granulocytes and macrophages. Vascular changes with perivascular edema and swelling of the endothelium were seen and a few neutrophilic granulocytes could be found in the vessel walls. No lymphocytic infiltration appeared. Severe morphologic changes observed after 44-48 h or at the time of complete rejection were characterized by severe interstitial hemorrhage, appearance of widespread necrosis and marked vascular changes with development of leukocytoclastic-like vasculitis, possibly with thrombosis. Only a few lymphocytes appeared. The findings were essentially different from those observed in allogeneic heart transplantations, where classical first-set allograft rejection was seen. In normal donor hearts and syngeneic transplanted hearts used as controls, no significant morphologic changes were demonstrated. On the basis of this study we consider xenogeneic acute rejection to be primarily of the humoral type.     

Muscarinic M(2) acetylcholine receptor distribution in the guinea-pig gastrointestinal tract

In the enteric nervous system, acetylcholine is the most common neurotransmitter to induce gastrointestinal smooth muscle contractions. Cholinergic signaling is mediated by muscarinic acetylcholine receptors on the surface of smooth muscle cells. Five different muscarinic receptor subtypes (M(1)-M(5)) have been identified and characterized, all of which belong to the superfamily of the G-protein-coupled receptor. The muscarinic M(2) acetylcholine receptor is the major muscarinic receptor subtype expressed by smooth muscle tissues in the gastrointestinal tract, where it is coexpressed with a smaller population of M(3) receptor. In this study, we examined the immunohistochemical distribution of the M(2) receptor using a specific antibody in the guinea-pig gastrointestinal tract. M(2) receptor-like immunoreactivity was mainly observed as associated with smooth muscle cells in the gastrointestinal tract. M(2) receptor-like immunoreactivity in smooth muscle cells was distributed throughout the cell membrane associated with caveolae. In the proximal colon, M(2) receptor-like immunoreactivity in the smooth muscle cells was weak. In the small intestine, interstitial cells of Cajal that possessed neurokinin 1 receptor-like immunoreactivity had intense M(2) receptor-like immunoreactivity. In the proximal colon, intramuscular and myenteric interstitial cells of Cajal exhibited M(2) receptor-like immunoreactivity. These findings indicate that, in the gastrointestinal musculature, M(2) receptors are distributed both in the smooth muscle cells and interstitial cells of Cajal, suggesting that the M(2) receptor elicits smooth muscle cell contraction and the interstitial cells of Cajal are the sites of innervation by enteric cholinergic neurons.     

Enteric neuropathology of the terminal ileum in patients with intractable slow-transit constipation

Slow-transit constipation is usually considered a colonic motor disorder. However, there is some evidence that abnormalities may be present in locations other than the colon. In particular, several studies have reported abnormal motor activity of the small bowel in these patients. We evaluated the neuropathological aspects of the terminal ileum in patients with slow-transit constipation to see whether abnormalities are present that may explain an abnormal motility of the small intestine. Specimens of the terminal ileum were obtained from 16 female patients (age range, 42-76 years) with slow-transit constipation undergoing surgery for intractable symptoms. Fifteen age- and sex-matched controls were used for comparison. Histologic and immunohistochemical evaluation of the myenteric plexus and the smooth muscle of the proximal ileal resection margin was carried out by means of hematoxylin and eosin, trichrome and periodic acid-Schiff stain, neuron-specific enolase, S-100, CD117, CD34, anti-alpha-actin, desmin, and vimentin antibodies. The patient group displayed a significantly reduced number of glial cells, compared with controls, in both the submucosal and the myenteric plexus. Only 1 of the 3 populations of interstitial cells of Cajal (that associated with the deep muscular plexus) was decreased in patients. No differences were found between patients and controls concerning ganglia neurons, fibroblast-like cells, enteric neurons, apoptotic phenomena, and smooth muscle. Patients with slow-transit constipation display neuropathological abnormalities of the terminal ileum to a lesser extent than those we previously found in the colon, which might explain the abnormal motor aspects sometimes found in these patients.     

糖尿病性胃轻瘫调节胃生理功能的相关组织细胞研究

糖尿病性胃轻瘫存在调节胃正常生理状态的几种关键组织细胞异常,包括胃自主神经支配异常,Cajal间质细胞受损和胃体肌壁巨噬细胞的变化等方面。巨噬细胞可能是引起其他类型细胞潜在损伤的关键细胞类型。本文对糖尿病性胃轻瘫调节胃生理状态的异常组织细胞予以分析,旨在指导临床治疗。