SD大鼠断奶后肠道菌群及肠道形态的变化

目的通过对断奶日龄不同的SD大鼠肠道菌群和肠道形态学指标变化的观察研究,为临床上研究肠道相关性疾病提供参考数据。方法选取断奶日龄为21 d的SD大鼠60只,雌雄各半,分别在断奶后第0、7、14、21、28天测定4种肠道正常菌群及肠道黏膜形态变化。结果SD大鼠断奶后不同时间点,不同肠段内大肠杆菌、双歧杆菌、乳酸杆菌和葡萄球菌呈现不同的变化规律,且断奶后第7天肠道细菌移位率明显提高,同时断奶后不同时间点,大鼠不同肠段黏膜厚度、肌层厚度、绒毛长度和宽度都呈现上升趋势。结论断奶后第7天和14天,SD大鼠肠道菌群和肠道形态学变化明显,且易发生肠道细菌移位。     

哺乳动物肠上皮屏障中非编码RNAs的调控作用

哺乳动物肠上皮是一种拥有快速自我更新能力的组织,在维持机体免疫稳态与肠道应激后的损伤修复中发挥重要作用。源于隐窝底部的多能肠干细胞不断进行增殖、迁移与分化,并沿隐窝 绒毛轴向上移动,从而维持肠上皮完整性。该过程受严格而复杂的基因调控网络参与。越来越多的数据表明,肠上皮完整性受到广泛的非编码RNA的调控,主要包括肠黏膜再生、保护与上皮屏障功能等方面。本文重点讨论了两类非编码RNA(包括microRNAs和lncRNAs)转录后调控肠上皮屏障功能的研究进展。其中,miR-503、miR-146和lnc-uc.173、lnc-SPRY4-IT1、lnc-plncRNA1、lnc-Gata6等,能够促进肠黏膜的更新,增强上皮屏障功能;相反,miR-222、miR-29b、miR-195和lnc-H19与lnc-BC012900等,抑制肠上皮再生并破坏肠上皮屏障功能。miRNAs、mRNAs与lncRNAs间构成复杂的分子网络,共同调控肠上皮稳态。深入研究与肠上皮相关的miRNAs和IncRNAs分子及其作用机制,探寻引起肠黏膜炎症的关键分子靶标,为肠道炎症临床诊治提供新方向与新方法。     

Intestinal subepithelial myofibroblasts support in vitro and in vivo growth of human small intestinal epithelium

The intestinal crypt-niche interaction is thought to be essential to the function, maintenance, and proliferation of progenitor stem cells found at the bases of intestinal crypts. These stem cells are constantly renewing the intestinal epithelium by sending differentiated cells from the base of the crypts of Lieberkühn to the villus tips where they slough off into the intestinal lumen. The intestinal niche consists of various cell types, extracellular matrix, and growth factors and surrounds the intestinal progenitor cells. There have recently been advances in the understanding of the interactions that regulate the behavior of the intestinal epithelium and there is great interest in methods for isolating and expanding viable intestinal epithelium. However, there is no method to maintain primary human small intestinal epithelium in culture over a prolonged period of time. Similarly no method has been published that describes isolation and support of human intestinal epithelium in an in vivo model. We describe a technique to isolate and maintain human small intestinal epithelium in vitro from surgical specimens. We also describe a novel method to maintain human intestinal epithelium subcutaneously in a mouse model for a prolonged period of time. Our methods require various growth factors and the intimate interaction between intestinal sub-epithelial myofibroblasts (ISEMFs) and the intestinal epithelial cells to support the epithelial in vitro and in vivo growth. Absence of these myofibroblasts precluded successful maintenance of epithelial cell formation and proliferation beyond just a few days, even in the presence of supportive growth factors. We believe that the methods described here can be used to explore the molecular basis of human intestinal stem cell support, maintenance, and growth.     

哺乳动物肠上皮屏障中非编码RNAs的调控作用

哺乳动物肠上皮是一种拥有快速自我更新能力的组织,在维持机体免疫稳态与肠道应激后的损伤修复中发挥重要作用。源于隐窝底部的多能肠干细胞不断进行增殖、迁移与分化,并沿隐窝 绒毛轴向上移动,从而维持肠上皮完整性。该过程受严格而复杂的基因调控网络参与。越来越多的数据表明,肠上皮完整性受到广泛的非编码RNA的调控,主要包括肠黏膜再生、保护与上皮屏障功能等方面。本文重点讨论了两类非编码RNA(包括microRNAs和lncRNAs)转录后调控肠上皮屏障功能的研究进展。其中,miR-503、miR-146和lnc-uc.173、lnc-SPRY4-IT1、lnc-plncRNA1、lnc-Gata6等,能够促进肠黏膜的更新,增强上皮屏障功能;相反,miR-222、miR-29b、miR-195和lnc-H19与lnc-BC012900等,抑制肠上皮再生并破坏肠上皮屏障功能。miRNAs、mRNAs与lncRNAs间构成复杂的分子网络,共同调控肠上皮稳态。深入研究与肠上皮相关的miRNAs和IncRNAs分子及其作用机制,探寻引起肠黏膜炎症的关键分子靶标,为肠道炎症临床诊治提供新方向与新方法。     

多糖对肠道功能调节作用的研究进展

肠道是机体重要的消化器官,亦是共生微生物群的主要寄居场所,在维持机体正常生命活动如免疫和内分泌功能中发挥着重要作用。 肠道功能紊乱与疾病的发生以及发展过程密切相关。近年来,多项研究结果显示,多糖具有肠道功能调节作用,包括通过作用于肠道黏膜 参与机体免疫过程、保护肠道屏障结构和功能的完整性、调节肠道菌群组成以及刺激肠道内分泌。从伴随疾病过程中的肠道功能紊乱的角度, 对多糖调节肠道功能的作用机制进行综述。     

肠黏膜屏障与肠道菌群的相互关系

摘要：人类肠道中微生物群与肠道环境相互作用以维持机体健康。肠黏膜屏障主要由黏液层、肠道菌群、肠道免疫系统和肠上皮细胞本身的完整性等构成。肠道作为直接与大量菌群接触的器官,其屏障功能在肠道健康中的作用尤为显著。肠道菌群与肠道屏障相互作用,保持肠道菌群与肠道屏障相对稳定,肠道菌群参与肠道免疫反应的建立,共同建立机体天然防御系统,在保持肠道免疫的动态平衡中具有重要作用。当两者之间的平衡被打破时,可诱发功能性胃肠病（如肠易激综合征）及免疫相关性疾病（如炎症性肠病）。本文主要阐述肠黏膜屏障与肠道菌群之间的相互关系以及与肠道屏障功能障碍相关的肠道疾病。     

痛泻要方对肝气乘脾泄泻小鼠肠道微生物活度的影响

目的探讨痛泻要方对肝气乘脾泄泻小鼠肠道微生物活度的影响,为痛泻要方通过调节肠道微生物治疗肝气乘脾泄泻提供实验基础和理论依据。方法将25只SPF级雄性昆明小鼠随机分为正常组10只和模型组15只,造模成功后,随机选取正常组和模型组动物各5只,在无菌环境下提取肠道内容物和肠黏膜,剩余模型动物随机分为自然恢复组和治疗组各5只,治疗成功后处死各组动物提取肠道内容物和肠黏膜。用荧光素二乙酸法测定各样品中微生物活度。结果肝气乘脾泄泻造模小鼠肠道内容物微生物活度高于正常组,与正常组相比差异有统计学意义(P=0.01),而模型组小鼠肠黏膜微生物活度降低,与正常组相比差异有统计学意义(P=0.01)。痛泻要方治疗组和自然恢复组小鼠肠道内容物微生物活度均降低,与正常组相比差异无统计学意义(P>0.05),治疗组和自然恢复组小鼠的肠黏膜前段和后段均与正常组差异有统计学意义(P=0.001),肠黏膜中段自然恢复组与正常组差异有统计学意义(P=0.043),而治疗组与正常组没有差异。结论肝气乘脾泄泻造模使肠道内容物微生物活度增加,而使肠黏膜微生物活度降低。痛泻要方能够使肝气乘脾泄泻小鼠肠道内容物中微生物活度降低,恢复至正常水平,增加肠黏膜中段微生物活度,对肠黏膜后段微生物活度增加作用更显著。     

鸡肠道微生物菌群的建立发育、分布和生理学意义

鸡的胃肠道具有复杂的微生物菌群,该微生物菌群与宿主的肠道和整体健康密切相关,为了全面揭示鸡肠道微生物菌群的组成及其功能,本文对鸡肠道微生物菌群的建立发育、各肠段群落的分布及其生理学意义进行综述,从而为鸡肠道功能菌株的分离及有效利用,合理调控微生物菌群-宿主相互作用,提高饲料转化率和改善肠道健康提供理论依据。     

Research progress on the regulation mechanism of probiotics on the microecological flora of infected intestines in livestock and poultry

The animal intestine is a complex ecosystem composed of host cells, gut microbiota and available nutrients. Gut microbiota can prevent the occurrence of intestinal diseases in animals by regulating the homeostasis of the intestinal environment. The intestinal microbiota is a complex and stable microbial community, and the homeostasis of the intestinal environment is closely related to the invasion of intestinal pathogens, which plays an important role in protecting the host from pathogen infections. Probiotics are strains of microorganisms that are beneficial to health, and their potential has recently led to a significant increase in studies on the regulation of intestinal flora. Various potential mechanisms of action have been proposed on probiotics, especially mediating the regulation mechanism of the intestinal flora on the host, mainly including competitive inhibition of pathogens, stimulation of the host's adaptive immune system and regulation of the intestinal flora. The advent of high-throughput sequencing technology has given us a clearer understanding and has facilitated the development of research methods to investigate the intestinal microecological flora. This review will focus on the regulation of probiotics on the microbial flora of intestinal infections in livestock and poultry and will depict future research directions.     

The role of intestinal microbiota and its metabolites in intestinal and extraintestinal organ injury induced by intestinal ischemia reperfusion injury

Intestinal ischemia/reperfusion (I/R) is a common pathophysiological process in clinical severe patients, and the effect of intestinal I/R injury on the patient''s systemic pathophysiological state is far greater than that of primary intestinal injury. In recent years, more and more evidence has shown that intestinal microbiota and its metabolites play an important role in the occurrence, development, diagnosis and treatment of intestinal I/R injury. Intestinal microbiota is regulated by host genes, immune response, diet, drugs and other factors. The metabolism and immune potential of intestinal microbiota determine its important significance in host health and diseases. Therefore, targeting the intestinal microbiota and its metabolites may be an effective therapy for the treatment of intestinal I/R injury and intestinal I/R-induced extraintestinal organ injury. This review focuses on the role of intestinal microbiota and its metabolites in intestinal I/R injury and intestinal I/R-induced extraintestinal organ injury, and summarizes the latest progress in regulating intestinal microbiota to treat intestinal I/R injury and intestinal I/R-induced extraintestinal organ injury.     

氧化应激对肠屏障功能障碍发病的影响

机体累积过量的活性氧自由基所导致的氧化应激是多种肠道疾病发生的共同病理生理基础。肠上皮细胞间的紧密连接是维持肠屏障功能的重要结构基础之一。近年来研究表明,氧化应激能通过多种途径破坏肠上皮细胞间的紧密连接,导致肠上皮屏障功能障碍。本文对蛋白激酶C、丝裂原活化蛋白激酶、蛋白质的修饰以及缺氧诱导因子-1(HIF-1)在肠屏障功能障碍中的作用机制进行简要概述,旨在为肠屏障功能障碍的治疗和预后提供新的思路。     

七味白术散对肠道酵母菌的抑促作用研究

目的：探讨七味白术散单味药对肠道酵母茵生长的影响,同时比较七味白术散复方传统汤剂与超微汤剂对肠道酵母茵的作用效果。方法：通过滤纸片法和比浊法测量药物的最低抑茵浓度及在测试浓度内的最佳促茵浓度。结果．：单味药人参和甘草对肠道酵母茵产生了抑制作用,其中人参的最低抑菌浓度为0．7936μg甘草的最低抑菌浓度为0．3949cOmE;茯苓、白术、葛根对肠道酵母茵产生了促进作用,葛根的促菌效果最好,茯苓次之;而木香和藿香对肠道酵母菌在本次研究中未表现出明显的抑促作用。七味白术散复方在低浓度下对肠道酵母茵产生了促进作用,且通过比较分析,七味白术散超微汤剂的促茵效果要优于传统汤剂（P〈0．01）。结论：人参和甘草对肠道酵母菌有抑制作用,茯苓、白术、葛根及七味白术散复方对肠道酵母茵有促进作用,且超微粉体的药物溶出率高于传统饮片,促菌效果好于传统饮片。     

Molecular analysis of the determination of developmental fate in the small intestinal epithelium in the chicken embryo

Determination of the developmental fate in the small intestinal epithelium of the chicken embryo has not been fully analyzed up to the present. This study was carried out to analyze the determination time of the developmental fate of the small intestinal epithelium under the influence of other mesenchymes. The small intestinal epithelium reassociated and cultivated with the proventricular or gizzard mesenchyme or the dermis expressed chicken intestinal fatty acid binding protein, sucrase and CdxA as occurs during the normal development of the small intestinal epithelium. The presumptive intestinal endoderm taken from an earlier stage embryo and associated and cultivated with the proventricular or gizzard mesenchyme, showed gene expression patterns which were the same as those found in normal development. However, when the dermis was associated, the epithelium expressed sonic hedgehog, but never expressed intestinal epithelial- or stomach epithelial-markers. These results indicate that the determination of the developmental fate in the small intestinal epithelium and acquisition of autodifferentiation potency occur at the early stage of the gut development. Moreover the presumptive intestinal endoderm needs the supportive influence of the gut mesenchyme in order to differentiate fully into the intestinal epithelium.     

肠道屏障损伤及细菌移位在焦虑抑郁症诱导退行性神经症中的机制

肠道屏障是脑-肠道交互作用的晴雨表。健全的肠道屏障对于维系肠道内微生态,抵御外源性病原体的侵入至关重要。焦虑抑郁症能够损害肠道屏障,破坏肠道菌群平衡。肠道屏障损伤引起肠道渗透性升高,肠腔细菌移位,促使外源性病原体进入血液循环和神经系统,启动系统性炎症反应。炎症反应对脑神经的损伤是诱导阿尔茨海默病和帕金森症发生、发展的主要原因。肠道屏障损伤还会破坏原有的肠道菌群结构,造成肠道菌群失调,不仅进一步损伤肠道屏障,还影响神经组织的结构和功能,是阿尔茨海默病和帕金森症形成的另一因素。此综述依据近年来的相关研究,从肠道屏障损伤的角度阐述了焦虑抑郁症触发退行性神经症的机制,强调维护肠道屏障功能在预防退行性神经疾病中具有重要的临床意义。     

Effects of somatostatin on intestinal circulation and oxygen consumption

The effects of intraarterial administration of somatostatin upon intestinal blood flow, intestinal capillary surface area, oxygen consumption and intestinal motor activity were measured in anesthetized dogs. Blood flow to the segment of distal ileum was measured with an electromagnetic blood flow meter, and arteriovenous oxygen difference (AVO2) was determined spectrophotometrically. Intestinal oxygen consumption was calculated as the product of AVO2 and total blood flow. The clearance of 86Rb was measured to estimate the density of the perfused intestinal capillaries. Changes in blood flow distribution were estimated from the distribution of radiolabelled microspheres. Intestinal motor activity was monitored from changes in intraluminal pressure. Somatostatin induced a dose-related decrease in intestinal blood flow, capillary surface area and intestinal oxygen consumption. A significant increase in intestinal motor activity was also observed. The data of this study indicate that somatostatin acts on smooth muscle of both arterioles and precapillary sphincters and results in a potent vasoconstriction in the intestinal microcirculation.     

A role for IL-22 in the relationship between intestinal helminths,gut microbiota and mucosal immunity

The intestinal tract is home to nematodes as well as commensal bacteria (microbiota), which have coevolved with the mammalian host. The mucosal immune system must balance between an appropriate response to dangerous pathogens and an inappropriate response to commensal microbiota that may breach the epithelial barrier, in order to maintain intestinal homeostasis. IL-22 has been shown to play a critical role in maintaining barrier homeostasis against intestinal pathogens and commensal bacteria. Here we review the advances in our understanding of the role of IL-22 in helminth infections, as well as in response to commensal and pathogenic bacteria of the intestinal tract. We then consider the relationship between intestinal helminths and gut microbiota and hypothesize that this relationship may explain how helminths may improve symptoms of inflammatory bowel diseases. We propose that by inducing an immune response that includes IL-22, intestinal helminths may enhance the mucosal barrier function of the intestinal epithelium. This may restore the mucosal microbiota populations from dysbiosis associated with colitis and improve intestinal homeostasis.     

大承气汤对MODS时肠道细菌微生态学影响的实验研究

目的探讨多器官功能不全综合征(MODS)大鼠肠道细菌微生态的变化及其与肠源性内毒素血症和细菌易位的关系,并观察大承气汤的影响。方法32只SD大鼠随机分成4组,对照组、模型组、大承气组和氨苄青霉素组。腹腔注射无菌酵母多糖A制备大鼠MODS模型。各组动物于造模后48 h无菌操作抽取外周静脉血和门静脉血进行内毒素含量测定;取肠系膜淋巴结进行细菌定量培养,取回肠和盲肠内容物进行肠腔内游离内毒素测定;取盲肠内容物进行肠道细菌微生态学分析。结果模型组外周血和门静脉血内毒素水平以及肠腔内游离内毒素含量均明显高于对照组(P<0.05);与对照组相比,模型组肠道菌群出现明显变化。肠球菌、肠杆菌数量明显增加,而双歧杆菌和乳酸杆菌数量出现显著下降,类杆菌数量亦出现明显下降(P<0.05)。模型组厌氧菌总数明显下降而需氧菌总数明显增加,同时厌氧菌总数/需氧菌总数的比值和B/E比值呈相应下降,发生倒置(P<0.05);正常对照组未发现肠道细菌向肠系膜淋巴结的易位,而模型组细菌易位阳性率是83.33%(P<0.05)。与模型组相比,大承气汤组上述各指标均出现明显变化(P<0.05);抗生素组作用不明显(P>0.05)。结论MODS时大鼠肠道细菌微生态出现明显变化,发生肠源性内毒素血症和细菌易位。大承气汤可以调整肠道菌群,恢复肠道微生态平衡,增加机体定植抗力,防治细菌易位和内毒素血症。     

肠道菌群在机体免疫调节功能中的作用

肠道菌群被称为是人体的一个重要"器官",具有数量庞大、种类繁多等特点,对人体具有重要的生理与病理意义。肠道菌群对机体免疫功能的影响日益受到广泛关注。本文主要就肠道菌群对肠道形态及功能、肠道黏膜免疫系统以及肠道外免疫系统三个方面的影响进行综述。     

肠道微生物对肠道屏障功能完整性的维护机制研究概况

肠道微生物群是一个稳定且复杂的生态系统,可以通过形成菌膜屏障或促进肠道上皮细胞增殖分化等方式形成保护屏障,并在肠道病原菌感染和威胁期间维持和促进免疫稳态中起积极作用。本文重点叙述宿主-肠道微生物相互作用过程中抗病原菌感染的方式,以及肠道微生物参与合成抗菌化合物抵御肠道病原菌入侵和威胁的机制,为调控肠道微生物解决临床胃肠道疾病及其相关症状提供理论参考依据。     

胃粘膜肠上皮化生SC3A的免疫组织化学研究

应用免疫组织化学ＡＢＣ方法等检测６２ 例胃良、恶性病变伴肠化组织中单克隆抗体ＳＣ３Ａ的表达及意义。结果： 癌旁肠化硫酸粘液阳性率明显较良性病变伴肠化高; 硫酸粘液阳性组肠化ＳＣ３Ａ阳性率明显高于硫酸粘液阴性组; 而且ＳＣ３Ａ 阳性率在酸性粘液阳性组胃癌明显高于酸性粘液阴性组; 硫酸粘液阳性组胃癌明显高于硫酸粘液阴性组。提示结肠型肠化可能与肠型胃癌的发生有一定关系