大鼠胃肠道Cajal间质细胞的超微结构研究

目的 明确大鼠胃肠道Cajal间质细胞的超微结构特点。方法 选用健康成年雄性SD大鼠的胃窦、小肠、结肠组织，进行透射电镜观察。结果 大鼠Cajal间质细胞的主要结构特点为：完整的基膜，丰富的基膜，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，异染色质较多，沿核膜分布，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。     

舒胃汤对功能性消化不良大鼠胃动素及胃窦Cajal间质细胞的影响

[目的]探讨舒胃汤对功能性消化不良( functional dyspepsia,FD)肝郁脾虚证大鼠胃排空、胃动素(Motilin,MOT)、胃窦Cajal间质细胞(interstitial cells of Cajal,ICO的影响.[方法]将60只大鼠随机分为舒胃汤低剂量组(低剂量组)、舒胃汤高剂量组(高剂量组)、木香顺气丸组(中成药组)、莫沙必利组、对照组、模型组,每组10只.采用夹尾刺激方法制造FD模型,造模后第3天各组给予相应药液灌胃,对照组、模型组给予蒸馏水灌胃,持续14d.实验结束后检测胃排空,免疫组化法检测MOT水平,电镜观察胃窦ICC超微结构.[结果]模型组与对照组大鼠比较胃排空延迟,MOT水平明显升高(均P＜0.05).与模型组比较,给药各组大鼠胃排空改善(均P＜0.05);高剂量组和莫沙必利组MOT降低(均P＜0.05);透射电镜观察高剂量组胃窦部ICC与模型组比较结构明显改善,接近对照组.[结论]舒胃汤能够促进胃排空,下调MOT水平,改变胃窦ICC超微结构,恢复胃肠道运动功能可能是舒胃汤治疗FD的作用机制之一.     

胃电刺激对大鼠胃窦肌间神经丛Cajal间质细胞超微结构的影响

背景：前期研究发现胃窦肌间神经丛Caial间质细胞（ICC-MY）数量增多参与了长时程长脉冲胃电刺激（GES）对胃慢波的调控。目的：观察不同时程长脉冲GES对大鼠胃窦ICC-MY数量和超微结构的影响,进一步探讨GES调控胃慢波的可能机制。方法：建立Wistar大鼠GES模型。将模型大鼠分为3组,GES1组和GES2组选用适宜的刺激参数控制胃慢波,对照组不予GES。GES1组仅予刺激一次;GES2组每天刺激一次,连续20 d。完成GES后处死大鼠,取胃窦组织,行透射电子显微镜观察。结果：GES1组胃窦ICC-MY数量与对照组相比未见明显变化,GES2组ICC-MY数量较GES1组和对照组明显增多。GES1组和GES2组ICC胞质内线粒体和核糖体均较对照组增多。GES1组ICC突起与周围平滑肌细胞（SMC）直接相连,GES2组ICC与周围SMC紧密相连,对照组ICC与周围SMC之间未见明显连接。结论：胃窦ICC-MY数量和超微结构改变参与了长时程长脉冲GES对胃慢波的调控。     

舒胃方调控SCF/c-Kit通路对功能性消化不良大鼠胃排空功能及Cajal间质细胞的影响

目的:探讨舒胃方调控干细胞生长因子(stem cell factor, SCF)/c-Kit通路对功能性消化不良(functional dyspepsia, FD)大鼠胃排空功能及Cajal间质细胞(interstitial cells of Cajal, ICCs)的影响并进行分子对接,分析其作用机制。方法:32只SD级大鼠,随机取8只为空白组,另外24只通过多因素应激干预法建立FD大鼠模型,随机分为模型组、莫沙比利组及舒胃方组。光学显微镜观察大鼠胃窦组织;酚红法检测大鼠胃排空率;透射电镜观察大鼠ICCs的超微结构;ELISA法检测大鼠腹主动脉SCF含量;Western Blot检测大鼠胃窦组织SCF、c-Kit蛋白的表达;对舒胃方中所含活性成分进行收集与筛选,并对“有效成分-靶点”拓扑分析所得度值较高的有效成分进行分子对接。结果:各组大鼠胃壁组织结构完全,胃黏膜上皮完整,胃腺体结构和排列规整,未见明显炎性细胞浸润。空白组大鼠ICCs超微结构清晰,数量多,体积大,呈圆形、梭形,细胞核占比多,细胞质占比少,线粒体、内质网、核糖体多;模型组大鼠ICCs超微结构改变,数量少,体积小,线粒体...     

糖尿病大鼠肠道Cajal间质细胞结构变化的研究

目的：明确糖尿病时肠道Cajal间质细胞超微结构的变化。方法：对12周四氧嘧淀糖尿病大鼠模型的小肠、结肠组织进行透射电镜观察。结果：实验观察发现糖尿病时Cajal间质细胞与其他细胞间的缝隙连接显著减少、结构破坏、连接松散;线粒体肿胀、空泡样变、溶解;胞质广泛溶解,细胞器减少。结论：糖尿病时肠道Cajal间质细胞的超微结构发生了显著的变化,这些结构的改变与其功能的改变密切相关,Cajal间质细胞超微结构的变化很可能是糖尿病胃肠功能紊乱的病因之一。     

糖尿病大鼠胃Cajal间质细胞超微结构的改变

糖尿病并发上消化道动力异常十分常见，但其发病机制尚未完全阐明。Cajal间质细胞广泛分布于胃肠道，有着重要的生理功能，目前认为Cajal间质细胞是胃肠道运动的起搏细胞，它不仅能产生节律性慢波电活动，还能调节神经递质的传递。本实验中，我们用大鼠建立糖尿病动物模型，记录其胃电活动，观察糖尿病病变大鼠胃Cajal间质细胞的超微结构改变，探讨糖尿病胃电节律紊乱原因。     

糖尿病大鼠胃部Cajal间质细胞超微结构变化的研究

研究发现 ,Ｃａｊａｌ间质细胞是胃肠道慢波的起搏细胞 ,国外已有研究发现很多胃肠功能紊乱性疾病的发病机制与Ｃａｊａｌ间质细胞的分布与结构变化有关。本研究以 12周糖尿病大鼠为研究对象 ,对其胃部Ｃａｊａｌ间质细胞在电镜下超微结构的变化进行了观察 ,以进一步明确糖尿病胃轻瘫的发病机制。一、材料和方法1 .实验动物 :健康成年雄性ＳＤ大鼠 8只 ,体重 2 5 0～ 30 0ｇ ,随机分为两组 :糖尿病组和正常对照组各 4只。2 .糖尿病大鼠模型的建立[1] :①糖尿病组 :给予四氧嘧啶 4 5ｍｇ/ｋｇ经舌下静脉一次注射 ,1周后测定血糖浓度≥2 0 0ｍ…     

干细胞因子对糖尿病结肠Cajal间质细胞的影响

目的 探讨糖尿病(DM)小鼠干细胞因子(SCF)对结肠Cajal间质细胞(ICC)异常的影响.方法 40只雄性C57/BL6小鼠分为正常对照组,DM组、正常+抗-SCF组、DM+SCF组,每组10只.DM成模后6周处死小鼠,以流式细胞仪、透射电镜、Western印迹法观察近端结肠组织中ICC的变化,以Western印迹、酶联免疫吸附实验(ELISA)检测结肠组织和血清中SCF的表达情况.结果 DM小鼠血清和近端结肠组织中SCF均明显降低,伴有结肠中ICC数量减少、超微结构显著破坏;正常+抗-SCF组,血清和近端结肠组织中SCF均明显降低,并伴有结肠中ICC数量减少、超微结构显著破坏(类似DM组);DM+SCF干预后,血清和近端结肠组织中SCF水平增高,ICC的数量以及超微结构病变得到显著改善.结论 DM小鼠血清和近端结肠组织中SCF水平的下降,可能是DM结肠中ICC数量减少和超微结构破坏的原因;外源性SCF能改善DM相关的胃肠道ICC病变.     

慢性束缚水浸应激对大鼠胃窦Cajal间质细胞超微结构的损伤

目的:研究不同时程慢性束缚水浸应激对大鼠胃窦Cajal间质细胞(ICC)超微结构的损伤,量化分析细胞内不同超微结构的损伤程度.方法:48只雄性SD大鼠随机分为6组,即实验3d、7 d、28 d组和对照3 d、7 d、28 d组,每组8只.实验组每日给予束缚水浸1 h,对照组自由摄食饮水;禁食12 h后分别于第4、8、29天晨脱颈处死,每组中的3只大鼠被各取胃窦组织2块放入3%戊二醛中固定并送电镜室镜检.将损伤的严重程度分成0-3级并以此标准计分并计算.结果:不同应激时间组大鼠胃窦ICC的核周间隙、基膜、内质网的损伤严重程度无明显差别.缝隙连接和线粒体的损伤积分有明显差异,胞质溶解、粗面内质网减少、核异常程度积分有极显著性差异:量化分析显示:随着应激时间的延长,超微结构受损呈现逐渐加重的趋势,主要表现在缝隙连接、线粒体、胞质和粗面内质网等方面.结论:慢性应激可以导致大鼠胃窦ICC超微结构的损伤,不同细胞超微结构的损伤随应激的延长有所差别;量化分析可以显示不同细胞器受损伤的程度.     

不同时程慢性束缚水浸应激对大鼠胃窦Cajal间质细胞超微结构的影响

目的:研究不同时程慢性束缚水浸应激大鼠胃窦Cajal间质细胞(ICC)的超微结构改变.方法:♂ SD大鼠48只随机分为6组、即实验3、7、28 d组和对照3、7、28 d组,每组8只.实验组每日束缚水浸1 h,对照组自由摄食饮水;于实验第4、8、29天晨禁食12 h后脱颈处死.取胃窦组织2块放入3%戊二醛中固定并电镜下观察ICC超微结构.结果:所有对照组ICC的超微结构均无异常改变,试验3、7、28 d各组ICC的超微结构与同期对照组比较均有明显的损害,主要表现为ICC的缝隙连接减少、细胞器减少等,以肌内ICC(ICC-MY)和肌间ICC(ICC-IM)为主:随着应激时间的延长,ICC的超微结构受损逐渐加重.结论:慢性束缚水浸应激可以损伤大鼠胃窦ICC的超微结构.     

胰岛素、干细胞因子和Cajal间质细胞在糖尿病胃轻瘫中的作用

糖尿病胃轻瘫是糖尿病的常见并发症，严重影响患者的生活质量和血糖控制。胃肠道Cajal间质细胞在维持胃肠功能中发挥重要作用，糖尿病智组织中存在Cajal间质细胞数量和结构的异常改变，从而影响胃动力。胰岛素、干细胞因子对糖尿病胃肠道Cajal间质细胞的病变具有重要调控作用。本文就胰岛素、干细胞因子和Cajal间质细胞在糖尿病胃轻瘫中的作用作一综述。     

糖尿病结肠动力障碍时Cajal间质细胞和干细胞因子的变化以及胰岛素的干预效应

Cajal间质细胞（ICC）异常可能是糖尿病胃肠动力障碍的重要原因之一。目的：观察糖尿病结肠慢传输型动力障碍大鼠ICC及其Kit受体配体干细胞因子（SCF）的变化，以及胰岛素干预对结肠动力障碍和ICC的影响。方法：雄性Sprague—Dawley大鼠分为正常对照组、糖尿病模型组和不同剂量胰岛素（每天8、12、16U／kg）干预组。于成模第6、8、10周时分批处死各组大鼠，以免疫组化染色、蛋白质印迹法和电子显微镜观察近端结肠组织ICC的变化．以酶联免疫吸附测定（ELISA）和荧光定量聚合酶链反应（qPCR）检测血清和结肠组织SCF的表达。结果：糖尿病模型大鼠胃肠推进率显著降低，近端结肠组织ICC数量减少，超微结构破坏，结肠组织可溶型SCF（S-SCF）mRNA表达和血清S-SCF、胰岛素水平降低。小剂量胰岛素干预可显著改善糖尿病大鼠的胃肠推进率，增加ICC数量，逆转其超微结构改变：中、大剂量胰岛素干预则无明显作用。结论：糖尿病大鼠胰岛素分泌减少，使S-SCF表达降低，引起结肠组织ICC数量减少．结构破坏，可能是结肠慢传输型动力障碍的发生基础之一。小剂量胰岛素可改善糖尿病大鼠的ICC病变和结肠动力障碍。     

Interstitial cells of Cajal are present in human extrahepatic bile ducts

Background and Aims: Interstitial cells of Cajal (ICC) are distributed with smooth muscle throughout the gastrointestinal tract and are involved in regulating motility. ICC were recently discovered in the wall of the human gallbladder. This study sought to determine whether ICC are present in human bile ducts. Methods: Biliary tract samples were obtained from several sources: surgical specimens (n = 16, 11 women, mean age 61 years); archival post‐mortem specimen (n = 1, 86 years, man); and cadavers (n = 2, 68 and 80 years, men). Paraffin‐embedded sections (3 µm) from the gallbladder (fundus, body and neck) and both extrahepatic and intrahepatic bile ducts were investigated. A double immunofluorescence protocol using polyclonal and monoclonal c‐kit antibodies and mast cell tryptase was used to distinguish c‐kit‐positive cells with typical ICC morphology from c‐kit‐positive mast cells. Small bowel samples were used as positive controls. ICC in the gallbladder were confirmed by ultrastructural study. Results: c‐kit‐positive cells with characteristic ICC morphology were identified in the subepithelial and muscular layers of the gallbladder and extrahepatic bile ducts. They were most prominent within the muscle layer of the extrahepatic bile ducts where they were organized into loosely arranged laminae running parallel to circular smooth muscle fibers. ICC were not found in intrahepatic bile ducts. Conclusion: This study demonstrates for the first time that ICC are present in human extrahepatic bile ducts where they are more densely aggregated than in the gallbladder. This cellular network is likely to be involved in biliary tract motility and its related disorders.     

The Importance of Interstitial Cells of Cajal in the Gastrointestinal Tract

Gastrointestinal (GI) motility function and its regulation is a complex process involving collaboration and communication of multiple cell types such as enteric neurons, interstitial cells of Cajal (ICC), and smooth muscle cells. Recent advances in GI research made a better understanding of ICC function and their role in the GI tract, and studies based on different types of techniques have shown that ICC, as an integral part of the GI neuromuscular apparatus, transduce inputs from enteric motor neurons, generate intrinsic electrical rhythmicity in phasic smooth muscles, and have a mechanical sensation ability. Absence or improper function of these cells has been linked to some GI tract disorders. This paper provides a general overview of ICC; their discovery, subtypes, function, locations in the GI tract, and some disorders associated with their loss or disease, and highlights some controversial issues with regard to the importance of ICC in the GI tract.     

槟榔对小鼠结肠Cajal间质细胞形态学影响的研究

[目的]探讨槟榔对小鼠结肠Cajal间质细胞(ICC)超微结构的影响及其与肠神经的关系.[方法]60只小鼠随机分为4组,每组15只.对照组、甘草组、槟榔组及莫沙必利组每天分别给予等体积的0.85％氯化钠、甘草溶液(3.75 g/kg)、槟榔溶液(5 g/kg)、莫沙必利溶液(0.4 mg/kg)灌胃,15 d后透射电镜...     

自发性高血压大鼠肾髓质间质细胞内脂性分泌颗粒的研究

选用自发性高血压大鼠（SHR）和对照（WKY）大鼠各9只，雄性．4月龄．血压分别为211.68±6.63mmHg和126.46±2.21mmHg，取肾髓质划分为4个区，分别作光学及电境观察。组织经Levl液固定后，肾髓质间质细胞（RIC）胸浆内脂性颗粒呈黑色；图像分析结果证实SHR大鼠肾髓质各区所含脂性颗粒均较WKY者为少且细小，特别是1区2区内最为显著，本实验提示SHR大鼠RIC内脂性颗粒较少，可能显其高血压发生发展的因素之一。     

Interstitial cells of Cajal in the human fetal small bowel as shown by c-kit immunohistochemistry

Background—Interstitialcells of Cajal (ICCs) express the tyrosine kinase receptor c-kit, whichis required for their development and spontaneous pacemaker activity inthe bowel. From murine models it has been proposed that ICCs do notdevelop until after birth, but more recent findings indicate that c-kitis expressed early in the embryonic period. The temporal development ofICCs in the human gut remains unknown.
Aim—To investigateICCs in the human fetal small bowel using c-kit immunohistochemistry.
Subjects—Small bowelspecimens were obtained at post mortem examination of 16 fetuses andnine neonates, eight of whom were premature, born at gestational agesof 13 to 41 weeks, without gastrointestinal disorders.
Methods—Immunohistochemicalanalysis was performed on material fixed in formalin and embedded inparaffin. The specimens were exposed to antibodies raised against c-kit(an ICC marker) and neurone specific enolase (a general neuronalmarker). The ABC complex method was used to visualise binding ofantibodies to the corresponding antigens.
Results—c-kitimmunoreactive cells were visualised from 13 weeks of gestation. Theimmunoreactivity was mainly localised in association with the myentericplexus. From about 17-18 weeks of gestation, the ICCs formed a layeralong the myenteric plexus, whereas this layer appeared to be disruptedat 13-16 weeks of gestation.
Conclusions—ICCs arec-kit immunoreactive at least from a gestational age of 13 weeks inthe human fetal small intestine. From 17-18 weeks of gestation untilbirth, they form a continuous layer around the myenteric ganglia.

Keywords:interstitial cells of Cajal; c-kit; myentericplexus; human; fetal; development

     

Control of gallbladder contractions by cholecystokinin through cholecystokinin-A receptors on gallbladder interstitial cells of Cajal

AIM： To identify the cholecystokinin （CCK）-A receptors （CCK-AR） on the guniea pig gallbladder interstitial cells of cajal （ICC） and to study CCK-8 induced gallbladder muscle strip contractions through the CCK-AR.
METHODS： The existence of CCK-AR was examined by immunohistofluorescence on sectioned tissue and cultured cells. In vitro contractile response of guinea pig gallbladder muscle strips and the strips with ICC removed were also studied with CCK-8 receptors added.
RESULTS： In tissue sections, intensely CCKAR- immunoreactive interstitial cells were found mainly in the muscular layers. In cultured cell sections, distinctive double staining of C-kit and CCK-AR ICCs were found. When we removed the ICC of the gallbladder, CCK-8 induced muscle strip contraction dose response curve significantly shifted to the right.
CONCLUSION： We proved that both the existence of CCK-AR on the guinea pig gallbladder ICC and CCK evoked contraction are mediated through direct action on CCK-AR on the gallbladder ICC.     

舒胃汤对功能性消化不良大鼠Cx43蛋白的分布及Cajal间质细胞的修复与再生的影响

[目的]观察舒胃汤对功能性消化不良（FD）肝郁脾虚型大鼠Cx43蛋白的分布及Cajal间质细胞的修复与再生的影响,探讨舒胃汤治疗FD的机制.[方法]将72只大鼠随机分为对照组、模型组、舒胃汤低剂量组（舒低组）、舒胃汤中剂量组（舒中组）、舒胃汤高剂量组（舒高组）和莫沙比利组（西药组）,每组各12只.舒低组、舒中组、舒高组分别给予舒胃汤0.767 g/ml、1.534 g/ml、3.068 g/ml,西药组予莫沙必利1.37 mg/kg.采用复合病因造模（慢性束缚应激十过度疲劳十饮食失节）,造成FD肝郁脾虚证大鼠模型.造模后第3天各组给予相应药液,对照组和模型组每日予以蒸馏水（10ml/kg）,均为1次/d,持续14 d.第15天处死取胃窦组织和小肠组织做免疫组织化学和荧光双染色观察Cx43蛋白的表达和ICC及神经纤维的形态.[结果]与对照组比较,模型组胃窦组织和小肠组织中Cx43蛋白阳性表达明显下降（P＜0.01）;与模型组比较,舒高组、舒中组和西药组胃窦组织和小肠组织中Cx43蛋白阳性表达明显升高（P＜0.01）;与对照组比较,模型组ICC超微结构损伤明显,胆碱能神经-ICC-SMC网络结构紊乱,ICC和神经纤维数目减少（P＜0.01）,荧光强度明显减弱（P＜0.01）;与模型组比较,舒高组、舒中组和西药组ICC超微结构较为正常完整,胆碱能神经-ICC-SMC网络基本完整,ICC和神经纤维数目明显增多（P＜0.01）,荧光强度明显加强（P＜0.01）.[结论]舒胃汤能够上调Cx43蛋白的表达,修复ICC和促进ICC的再生,增加神经纤维的数目,从而保持胆碱能神经-ICC-SMC网络结构的完整,恢复胃肠动力而有效治疗FD.