肠黏膜屏障功能检测的研究现状

肠黏膜屏障是指肠道能防止肠腔内有害物质如毒素或细菌穿过肠黏膜进入体内其他组织器官和血液循环的结构和功能总和。近年来随着基础医学研究的深入，人们逐渐认识到肠黏膜不仅仅有消化和吸收功能，而且具有重要的防御性屏障功能，发现肠道屏障功能障碍、肠内细菌及内毒素移位是导致SIRS、MODS，甚至MSOF的一个重要因素。肠道屏障功能已成为判断危重病人预后的一个重要指标，[第一段]     

肠黏膜屏障在1型糖尿病中的作用研究进展北大核心CSCD

1型糖尿病(T1DM)是儿童和青少年常见的以胰岛β细胞破坏和胰岛素缺乏为特征的自身免疫性疾病。近期研究表明,肠道菌群失衡和肠黏膜屏障变化与T1DM发生发展相关,但具体机制尚不清楚。本文就近年肠道菌群、肠黏膜屏障在T1DM中的作用研究进行综述,并探讨孕期治疗、粪菌移植、益生菌、短链脂肪酸治疗维持健康肠黏膜屏障改善T1DM的研究进展,为T1DM防治提供新方法。     

Notch信号通路在肠黏膜屏障中的研究进展

Notch信号通路是一种介导细胞与细胞之间信号级联反应的高度保守的通路。其对于多种细胞的分化、增值和凋亡具有调节作用。该信号通路的激活或失活在肠黏膜屏障中发挥着非常重要的作用。对指导各种疾病中所引起的肠黏膜屏障损伤的治疗提供新的视野和思路。     

自噬在肠黏膜屏障功能作用机制的研究进展

自噬是细胞通过膜囊泡结构降解胞质内大分子物质和受损细胞器维持机体稳态的生物学过程。在肠黏膜屏障功能发生障碍过程中,自噬对于维持肠上皮细胞的存活起关键性作用。负调控自噬可导致肠道炎性反应和肿瘤的发生。     

黏蛋白-2与肠黏膜屏障损伤的研究进展

黏蛋白-2(MUC2)是肠黏液层主要成分,覆盖于肠上皮细胞顶端,主要由杯状细胞分泌,在润滑肠道、为肠内抗菌蛋白及共生菌群提供黏附位点、抵御肠内致病菌及有害物质入侵等方面发挥着重要功能.近年来MUC2在肠道黏膜屏障损伤中的作用研究日趋受到学者重视,这也可能是肠黏膜屏障损伤的一个重要治疗突破口.     

危重症患者肠源性感染及肠管复苏

<正>肠管不仅是消化吸收的器官,肠黏膜本身也是机体十分重要的一道抗感染防御屏障。正常情况下,肠黏膜能够有效地阻止肠管中的细菌和内毒素侵入体内。在各种内因和外因作用下,危重症患者肠黏膜屏障功能破坏,肠管内细菌和内毒素侵入体内,在特定的条件下两者协同作用造成肠     

肠道微生态与肠道疾病

人类肠道微生态是一个包含大量肠道微生物的复杂生态系统,近年来研究发现肠道细菌过度繁殖可导致胃肠道动力失调及内脏神经敏感性改变,最终导致肠易激综合征的发生,而肠道菌群引起的肠粘膜异常免疫应答损伤被认为是炎症性肠病发病机制的关键所在,另外,肠道微生态还可过参与炎症性肠病的病理生理过程或直接代谢产生致癌物质影响肠道肿瘤的发生发展。由此我们发现,肠道微生态不仅参与了消化吸收、物质代谢等胃肠道基本生理过程,还直接关系到肠道疾病的发生。本文将就目前肠道微生态与肠道疾病的研究进展进行简单综述。     

细胞焦亡在肠黏膜屏障损伤机制中的作用

肠上皮细胞、免疫系统及微生物的相互联系维持肠黏膜屏障完整性和自我更新。肠黏膜屏障损伤易导致难以预测的严重疾病发生。细胞焦亡是一种由活化的半胱天冬酶切割Gasdermin家族蛋白介导的炎症细胞死亡形式,在急慢性疾病控制中发挥重要作用。病理生理状态下,细胞焦亡参与肠黏膜屏障损伤及异常免疫调节,最终导致多种肠道疾病发生。本文综述细胞焦亡在肠道感染、肠缺血再灌注、坏死性小肠结肠炎及炎症性肠病中的最新调控机制,针对此类肠道疾病提供新的有效治疗策略。     

分析患儿肠道内微生物的变化与轻度胃肠炎伴良性婴幼儿惊厥之间的关系

目的 分析轻度胃肠炎伴良性婴幼儿惊厥(BICE)和患儿肠道内微生物的变化间的相关性.方法 回顾分析2017年1月至2018年12月在我院诊治的BICE患儿40例,作为研究组,将2019年1月至12月我院诊治的40例单纯轻度胃肠炎患儿作为对照组,两组均行粪便轮状病毒抗原检测、相关病菌检测及肠黏膜屏障功能检测,记录试验数据,并进行比对分析.结果 研究组及对照组轮状病毒感染率分别为47.5％、15.0％;粪便内大肠杆菌、肠球菌、乳酸杆菌、双歧杆菌数量及DAO、D-乳酸、NO水平,研究组均高于对照组(P＜0.05)差异有统计学意义.结论 肠道微生物改变可影响BICE发生及发展,轮状病毒及肠内益生菌减少可促使BICE病情发展,损坏肠黏膜屏障功能.     

肠道菌群和"肠-肺"轴在脓毒症中的作用

肠道菌群是寄生在人体肠道内数量庞杂的微生物群。"肠-肺"轴是连接肠道和肺部的双向轴。肠道菌群和"肠-肺"轴参与了脓毒症的发生与发展。脓毒症发生时,肠黏膜屏障受损,肠道菌群失调,细菌移位,肺为最先发生损伤的器官,肺部感染也会导致肠道功能紊乱。     

Technical report: results of immunological tests on faecal extracts are likely to be extremely misleading.

Clinical investigation of gut immunity is difficult because of the need to study intestinal tissues or secretions directly. Others have reported that immunoglobulins, antibodies and cytokines can be detected in saline extracts of faeces. We have assessed the validity of this approach by measuring immunoglobulins, albumin, alpha 1-antitrypsin and isotype-specific antibodies in matched samples of faeces and whole gut lavage fluid. Results were compared as estimated output per day, and by using haemoglobin as a common reference substance. Samples were obtained from 10 patients with active inflammatory bowel disease and 10 with other benign GI diseases. For immunoglobulins, albumin and antibodies, the amount detected in faeces varied from < 0.01% to 35.5% (based on estimated daily output) and < 0.01% to 18.5% (based on haemoglobin) of the amount known to be produced in the gut from results of assays on whole gut lavage fluid (WGLF); there were significantly higher rates of recovery in faecal specimens from patients with active gut inflammation than from other patients. Detection rates and titres of specific antibody in faeces were even lower than those for immunoreactive IgA. These data indicate that immunological tests on saline extracts of faeces do not represent the true status of the gut humoral immune system, and such studies should be strongly discouraged.     

实验大鼠,实验小鼠肠道鞭毛虫种类和检索

我们对普通级SD大鼠和KM小鼠肠道内鞭毛虫分别作了观察,从大鼠检出10种肠道鞭毛虫:鼠唇鞭毛虫(Chilomastixbettencourti)、人肠滴虫(Enteromonashominis)、西蒙氏贾第虫(Giardiasimoni)、鼠六鞭虫(Hexamitamuris)、似单尾滴虫(Monocercomonoidiessp)、人五毛滴虫(Pentatrichomonashominis)、曲滴虫(Retortamonassp)、田鼠四毛滴虫(Tetratrichomonasmicroti)、微小三毛滴虫(Tritrichomonasminuta)和鼠三毛滴虫(Tritrichomonasmuris)。从小鼠检出8种肠道鞭毛虫:鼠唇鞭毛虫(Chilomastixbettencourti)、鼠贾第虫(Giardiamuris)、鼠六鞭毛虫(Hexamitamuris)、鼠八鞭毛虫(Octomituspulcher)、人五毛滴虫(Pentatrichomonashominis)、田鼠四毛滴虫(Tetratrichomonasmicroti)、微小三毛滴虫(Tritrichomonasminuta)、鼠三毛滴虫(Tritrichomonasmuris)。根据大鼠和小鼠肠道鞭毛虫的形态特征分别列出了检索表。     

Prebiotic effect of yacon (Smallanthus sonchifolius) on intestinal mucosa using a mouse model

Prebiotics are non-digestible but fermentable oligosaccharides that can influence the composition and the activity of some intestinal bacteria to promote the health of the host. Smallanthus sonchifolius (yacon) contains beta-1,2-oligofructans as the main saccharides and its roots are consumed in South American countries. The aim of the study was to evaluate the prebiotic property of yacon root flour. Its influence on the intestinal microbiota and gut immune system were evaluated using a mice model. The results show the prebiotic effects of yacon root flour, stimulating the growth of bifidobacteria and lactobacilli and the intestinal immune system with increases in IgA and different cytokines. Cells from the innate response were mainly involved in the effect of yacon root flour. T cells were also activated and able to induce IL-10 and IFNγ production. The long term administration of yacon root flour maintained the intestinal homeostasis without inflammatory effect regulated mainly through IL-10 and IL-4 regulatory cytokines.     

Distribution of human colonic dendritic cells and macrophages

To define the phenotype of intestinal dendritic cells and macrophages, resected colonic specimens were used to obtain lamina propria cell suspensions by EDTA treatment, then enzymatic digestion. The phenotype of dendritic cell-enriched suspensions was compared with that of macrophage-enriched populations by immunocytochemistry using the avidin-biotin-peroxidase (ABC) system and immunoelectron microscopy. Dendritic cells expressed HLA-DR (L243) and HLA-DQ-associated (RFD1) antigens and CD68 in a perinuclear distribution. Staining for S100 was weak or absent. Macrophages also expressed HLA markers (L243 and RFD1) and CD68. The 25F9 antigen was expressed strongly, whilst CD14 was absent from cells isolated from non-inflamed tissues. To determine their anatomic distribution, immunohistochemistry was performed using single- and double-labelling techniques (ABC ± alkaline phosphatase anti-alkaline phosphatase method). Mutually exclusive subsets of 25F9⁺ and S100⁺cells were seen: 25F9⁺ macrophages were concentrated in a band immediately beneath the luminal epithelium; S100⁺/HLA-DR⁺ dendritic cells formed a reticular network throughout the lamina propria and beneath the basement membrane of the crypts. This distribution suggests that macrophages may help regulate intestinal responses by acting as the first line of defence against the entry of luminal antigens. A breach of the macrophage ‘barrier’ by invading antigens may necessitate the recruitment of T cell responses by immunostimulatory dendritic cells.     

The involvement of intramural nerves in cholera toxin induced intestinal secretion

In previous reports we have suggested that nervous reflexes are involved in the pathophysiology of cholera secretion and that these nervous reflexes involve a cholinergic synapse and a neuron with vasoactive intestinal polypeptide (VIP) as neurotransmitter. These proposals were further analyzed in this study. Tetrodotoxin (TTX) and lidocaine applied on the serosal surface inhibited cholera secretion in segments of rat small intestine. Fluid absorption in control rats was not significantly changed. Hexamethonium given i. v. decreased cholera secretion in the cat. No additional inhibition of cholera secretion was observed after giving TTX close i. a. Furthermore, the intestinal secretion evoked by VIP was not influenced by hexamethonium given i. v. or TTX given close i. a. The present observations support the hypothesis of a role for nervous reflexes in cholera secretion. The results suggest that at least a major part of the proposed nervous reflex(es) in cholera have a cholinergic synapse. Furthermore, the VIP-ergic neuron is situated “distal” to the cholinergic neuron in the reflex(es) closer to the effector cells.     

Gastric cancer: problems in histogenesi

Intestinal metaplasia in the mucosa adjacent to a gastric carcinoma suggests that some carcinomas of the stomach might arise from metaplastic mucosa, as well as the existence of a gastric cancer with morphological features resembling intestinal mucosa. In this study, the extent of intestinal metaplasia of adjacent mucosa, the type of intestinal metaplasia (complete or incomplete), the degree of tumour differentiation, the type and quantity of mucins secreted by neoplastic cells and morphological features of the tumours were evaluated in 59 cases of gastric carcinoma. An analysis of the findings suggests that a carcinoma may arise in the stomach with features of association with incomplete metaplasia and histochemical and histological patterns which mimic carcinomas of the large intestine.     

Expression of cytotoxic molecules in intestinal T-cell lymphomas

Intestinal T-cell lymphoma (ITCL) represents a subgroup of peripheral T-cell lymphomas which is thought to arise from αβ intraepithelial T-lymphocytes. Since these lymphocytes may contain cytotoxic molecules, the question of whether this also holds true for ITCL arises. Twenty ITCL cases were examined for the presence of granzyme B, perforin, and T-cell-restricted intracellular antigen (TIA-1)/granule membrane protein of 17 kD (GMP-17). Two molecules with restricted expression in cytotoxic cells, granzyme B and perforin, were detected by immunocytochemistry and by in situ hybridization with an isotopically labelled RNA probe, respectively. Immunocytochemistry was also performed with the antibody 2G9, which recognizes two molecules, one expressed by cytotoxic cells (TIA-1) and the other found in granulocytes and cytotoxic cells (GMP-17). Granzyme B, TIA-1/GMP-17, and perforin were found in the neoplastic cells of 16/19 cases, 19/20 cases, and 16/17 cases, respectively, of ITCL, but not in the tumour cells of the control group, which consisted of intestinal B-cell lymphomas (five cases) and CD8-negative peripheral nodal T-cell lymphomas (six cases). At least one of these molecules was expressed in the tumour cells of all ITCL cases. 2G9 proved to be the most sensitive immunohistological marker, since reactivity with this antibody was not only observed in the highest number of cases, but also found in high numbers of neoplastic cells in positive cases. In conclusion, ITCL appears to show cytotoxic differentiation in all cases. In conjunction with immunophenotypic and genotypic data, our results support a uniform derivation of this tumour from intraepithelial αβ cytotoxic T-lymphocytes. © 1997 John Wiley & Sons, Ltd.     

NLRPs,microbiota, and gut homeostasis: unravelling the connection

Within the NOD‐like receptor (NLR) family, there are several NLRP (NLR family, pyrin domain‐containing) proteins that are involved in the formation of inflammasomes. These multi‐protein complexes are a key part of the network of cellular events required for secretion of the pro‐inflammatory cytokines IL‐1β and IL‐18. The NLRP3 inflammasome is the best‐characterized member of the family and has recently been implicated in gut homeostasis and determining the severity of inflammation in inflammatory bowel disease (IBD) and inflammation‐associated colorectal cancer. This led to the discovery that NLRP6 and NLRP12 also contribute to the maintenance of intestinal homeostasis and modulation of the gut microbiota, which in turn influences the intestine and distant organs. In this review, we bring together the latest data on the potential roles of NLRP family members in gut health and disease and identify the most pressing questions that remain to be answered to further our understanding of human diseases including IBD, inflammation‐associated cancers, and metabolic syndromes linked with obesity. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.