肠黏膜屏障在炎症性肠病的发病机制和治疗中的研究进展

炎症性肠病是一类反复发作的胃肠道慢性非特异性炎症,可见于任何年龄,发病率逐年升高,且发病机制仍不十分明确.肠黏膜屏障是指正常肠道具有的将肠腔内物质与机体内环境隔离的功能,它能够防止致病性抗原侵入黏膜下层组织,维持机体内环境的相对稳定和机体的正常生命活动.肠黏膜屏障功能的损伤与多种胃肠道疾病如炎症性肠病的发生密切相关.肠黏膜机械屏障、免疫屏障、生物屏障中的任一功能环节或其相互作用障碍,都有可能导致疾病的发生.明确肠黏膜屏障损伤在炎症性肠病发病中的具体机制,有效维持和修复肠黏膜屏障功能,有望成为治疗炎症性肠病的新策略.     

肠黏膜屏障的组成及其与肝损伤关系的研究进展

健康肠道的完整黏膜屏障是阻止物质易位的防线。目前动物模型和人类病理学研究证明,肠黏膜屏障功能的变化与肝病的发生和治疗有着密切的联系。该文就肠黏膜屏障的组成、其与肝损伤的关系以及潜在治疗靶点作一综述。     

Th17细胞在肠黏膜免疫中的作用

肠黏膜是人体最大的淋巴器官,它与呼吸道黏膜、泌尿生殖道黏膜等一起构成机体的第一道防御体系.肠黏膜经常抵御细菌、病毒、食物抗原、非甾体类抗炎药等的侵袭,若肠黏膜免疫系统遭受破坏,机体发生感染性疾病、自身免疫性疾病等.因此,肠黏膜免疫功能正常对机体的健康非常重要.Th17细胞是近年来发现的一类不同于Th1和Th2细胞的T细...     

小儿急性肠梗阻肠黏膜免疫屏障损伤及细菌移位的研究

目的 探讨小儿急性肠梗阻细菌移位及机制.方法 收集山西省儿童医院普外科2009年9月至2010年8月急性肠梗阻患儿共43例,依治疗方法分三组:肠切除肠吻合组(吻合组)22例,未切除肠管组14例,保守治疗组7例.另选择17例正常肠管及健康儿童10例分别作正常肠管、血清对照组.应用聚合酶链反应(PCR)定性检测细菌共有的16SrRNA和大肠杆菌特异性半乳糖苷酶基因BG;肠系膜淋巴结细菌培养;免疫组织化学方法检测肠黏膜固有层T细胞亚群、浆细胞计数;酶联免疫吸附试验(ELISA)定量检测血清TGF-β1浓度.结果 吻合组16SrRNA、BG阳性率分别为86.4%、72.7%,淋巴结培养阳性率77.3%;未切除肠管组16SrRNA、BG阳性率分别为64.3%、42.8%,淋巴结培养阳性率57.1%;保守治疗组16SrRNA、BG阳性率分别为57.1%、28.5%,正常肠管血清对照组16SrRNA、BG均未检出;吻合组肠黏膜固有层T细胞亚群、浆细胞数量均低于正常对照组;吻合组、未切除肠管组术前血清TGF-β1浓度均高于保守治疗组与对照组,术后7 d各组血清TGF-β1浓度与对照组比较无差异.结论 急性肠梗阻患儿肠黏膜固有层T细胞亚群、浆细胞均降低,引起肠黏膜免疫屏障破坏,同时TGF-β1水平升高,参与机体免疫抑制,免疫功能紊乱,加重黏膜免疫屏障破坏,增加机体易感性,促进了细菌移位.

Abstract：

Objective To investigate the mechanism of intestinal mucosal barrier damage and bacterial translocation in children with acute intestinal obstruction. Methods From September 2009 to August 2010, 43 patients with acute intestinal obstruction were treated at this center and recruited in this study. According to the treatment they underwent, they were divided into 3 groups: Group1 included 22 patients who were performed bowel resection and anastomosis. Group 2 had 14 patients who underwent surgeries but without bowel resection. Group 3 had 7 patients who were cured without surgery. The other 17 healthy bowels and 10 healthy children's serum were selected as normal controls.Polymerase chain reaction (PCR) was performed to examine β-lactosidase gene (BG) of E. coli and 16SrRNA gene. Bacteria in mesenteric lymph nodes were cultured. Immunohistochemical staining was used to indentify the T cell subsets and plasma cells in the lamina propria of mucosa. TGF-β1 in serum was quantified using enzyme-linked immunoabsorbent assay (ELISA). Results In group 1, 16SrRNA and BG were positive in 86. 4% and 72. 7% of the patients, respectively. Positive culture rate of E coli in mesenteric lymph nodes was 77. 3%. In group 2, 16SrRNA and BG positive rates were 64. 3% and 42. 8%, respectively. Positive culture rate of E coli in mesenteric lymph nodes was 57.1 %. In group 3,16SrRNA and BG positive rates were 57. 1 % and 28. 5%, respectively. 16SrRNA and BG were not detectable in normal control patients' serum and bowel. In the removed bowel, T cell subsets and plasma cells' population were significantly decreased compared with the control bowel. The serum TGF-β1 level of the patients underwent surgery was significantly higher than that of the healthy controls or the patients without surgery. But the difference was not significant between these 2 groups since 7 days after surgery. Conclusions In the children with acute intestinal obstruction, the reduction of T cell subsets and plasma cells in the lamina propria, increasing TGF-β1 in the serum are observed.These changes may be related to the damaged intestinal barrier and bacterial translocation.     

儿童肠道分节丝状菌年龄分布特征及其与肠黏膜免疫的关系

目的了解儿童肠道分节丝状菌（SFB）年龄分布特征及其与肠道黏膜免疫的关系。方法收集177例儿童的新鲜粪便及47例儿童肠镜检查时的回盲部肠液,采用RT-PCR法测定SFB,ELISA法测定其sIgA浓度。采用免疫组化方法测定23例儿童回肠末端黏膜IL-17A细胞数量和上皮内淋巴细胞数量及Th细胞分化相关的转录因子T-bet、FOXP3和ROR-γt的表达。结果儿童肠道SFB阳性率为19.2%（34/177）。趋势分析显示SFB阳性率随年龄增加呈降低趋势：0岁~、1岁~、2岁~、3岁~、4岁~、5岁~、6岁~、7~15岁分别为40%、47%、32%、15%、12%、13%、15%、4%（P < 0.001）。SFB阳性患儿（24例）的肠液sIgA浓度明显高于SFB阴性患儿（23例）（P < 0.01）。SFB阳性组（12例）回肠末端黏膜上皮细胞内淋巴细胞数量及转录因子T-bet、FOXP3和ROR-γt的表达与SFB阴性组（11例）的差异无统计学意义,而SFB阳性组回肠末端黏膜IL-17A细胞数量明显低于SFB阴性组（P < 0.05）。结论儿童SFB肠道定植与年龄相关,其中3岁以内婴幼儿SFB肠道定植率较高;SFB阳性者肠道sIgA分泌增加,回肠末端IL-17A细胞数量减少。     

肠黏膜先天性免疫的研究进展

肠道是人体免疫系统的重要组成部分，在接触大量的食物和消除病原微生物的过程中，肠黏膜屏障起了重大的作用。由生理性屏障结构和天然存在的抗微生物分子构成的先天性免疫，是宿主肠道防御系统的重要组成部分。     

肠黏膜先天性免疫的研究进展

肠道是人体免疫系统的重要组成部分,在接触大量的食物和消除病原微生物的过程中,肠黏膜屏障起了重大的作用。由生理性屏障结构和天然存在的抗微生物分子构成的先天性免疫,是宿主肠道防御系统的重要组成部分。     

胃肠黏膜屏障功能障碍及肠道细菌或内毒素移位对机体的影响

胃肠黏膜屏障功能障碍与肠道细菌和(或)内毒素移位,会导致机体不同的病症和内源性感染等,给临床医师对疾病的防治带来了难以预料的挑战.文章通过对胃肠黏膜屏障及其障碍、胃肠黏膜屏障与肠道细菌和(或)内毒素移位以及肠道内毒素移位对机体的影响等方面的探讨,使临床医师对疾病病理生理和防治等方面的知识和相关信息有更多的了解和认识,在临床工作中对遇到的临床问题会有更深和更广的理解和思考.     

富氢生理盐水对小肠缺血再灌注损伤大鼠肠黏膜屏障的保护作用

目的:探讨富氢生理盐水(HRS)对小肠缺血再灌注损伤(IIRI)大鼠肠黏膜屏障的影响。方法:将24只8周龄健康雄性SD大鼠按随机数字表法分为3组(每组8只)：假手术组、模型组和HRS组。HRS组大鼠在小肠缺血第30分钟时腹腔注射HRS(10 mL/kg);模型组大鼠在相同时间点腹腔注射9 g/L盐水(10 mL/kg)...     

益生菌在儿童变态反应性疾病中的防治作用

变态反应性疾病逐年升高的发病率已引起全球的关注,严重危害儿童健康,其共同发病机制是机体对常见的吸入性或食物性过敏原产生以特异性IgE介导的或者细胞介导的免疫反应。流行病学调查、粪便菌群分析和临床研究均提示,变态反应性疾病的发生、发展与早期肠道菌群的紊乱密切相关。益生菌可调节肠道免疫反应、增加上皮细胞屏障功能和抑制病原菌的粘附定植,恢复或重建肠道正常微生物群。随着人们对变态反应性疾病认识的加深,益生菌对其防治作用将越来越受到人们的重视。     

肠屏障功能障碍与新生儿坏死性小肠结肠炎

坏死性小肠结肠炎( necrotizing enterocolitis,NEC)是严重危及新生儿生命的消化系统疾病,是导致新生儿,尤其是早产儿死亡的重要病因之一。新生儿,尤其是早产儿维持肠屏障功能的作用元件发育不成熟,极易受损,不能有效形成上皮细胞间的紧密连接,无法早期形成正常肠道蠕动以及分泌型IgA的减少,因此各种致病因素极易诱发肠屏障功能障碍,导致菌群移位和败血症,造成严重的肠道损害甚至并发症。缺氧缺血、炎症反应、病原体感染均可造成肠机械屏障损害,微生态屏障建立延迟、免疫屏障发育的不成熟以及病理情况下的肠微循环障碍均参与NEC的发生。此外,miRNA在肠上皮细胞的分化、结构和屏障功能调控中也发挥重要作用。 NEC的组织病理改变是肠屏障功能障碍的结果,而肠屏障功能的损害则加重NEC的病理改变。因此,认识肠屏障功能障碍在 NEC发病过程中的作用,对于防治NEC意义重大。     

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目的探讨过敏性紫癜(HSP)患儿胃肠黏膜屏障变化。方法选取2007年9月至2008年8月昆明医学院第一附属医院儿科收治的过敏性紫癜患儿60例及正常儿童30名的血浆进行二胺氧化酶(DAO)、D-乳酸和内毒素检测。结果HSP组治疗前血浆DAO、D-乳酸及内毒素测定结果均升高,与正常对照组比较,差异有统计学意义(P<0.01)。有消化道症状HSP组治疗前血浆DAO、D-乳酸及内毒素测定结果,较无消化道症状HSP组及正常对照组高,两两比较差异有统计学意义(P<0.01)。HSP组治疗前后血浆DAO、D-乳酸及内毒素测定结果比较,除无消化道症状组差异无统计学意义外(t≤1.753,P>0.05),其他组均有统计学意义(t≥2.556,P<0.01)。结论HSP患儿存在肠黏膜屏障功能损伤,有消化道症状组较为明显,经治疗后其肠黏膜屏障存在修复过程。     

危重患儿肠屏障功能障碍时如何进行营养支持

肠黏膜屏障损伤是危重患儿常见的病理生理过程,可造成细菌及内毒素移位、肠源性感染,甚至发生多器官功能衰竭.早期诊断肠黏膜屏障损害,积极纠正肠屏障功能障碍,选择适当的营养方式将有助于提高疗效,改善患儿预后.本文就危重患儿肠屏障功能障碍的概念、诊断方法及营养支持的进展等做一阐述.     

Understanding and circumventing the blood-brain barrier

The blood-brain barrier presents a challenging obstacle to effective drug delivery to the central nervous system (CNS). Although biologically intended to protect the brain and spinal cord and provide a very stable fluid environment, the presence of a blood-brain barrier makes treatment of many CNS diseases difficult to achieve, as the required therapies cannot be delivered across the barrier in sufficient quantities or at all. Until relatively recently the blood-brain barrier was viewed largely as a physical barrier to diffusion, and the presence of tight junctions between endothelial cells simply prevented the passive diffusion of solutes from blood into the brain. Recent advances in cell and molecular biology have provided new insights into the function of the blood-brain barrier and it is now appreciated that, in addition to being a physical barrier, it is a complex transport and metabolic barrier and is a highly reactive and dynamic endothelium. Advances in understanding of the cell biology of the blood-brain barrier have opened new avenues and possibilities for improved drug delivery to the CNS. The challenges posed by the blood-brain barrier and the possibilities for overcoming them are reviewed.
Conclusion : Increased understanding of the molecular biology of the blood-brain barrier is now opening the way for new strategies to deliver drugs to the CNS.     

耐药基因蛋白在肿瘤组织血脑屏障的表达及临床意义

目的 通过检测多药耐药基因蛋白在儿童颅内肿瘤组织和正常脑组织的表达,探讨颅内肿瘤耐药机制.方法 采用免疫组织化学技术检测30例儿童颅内肿瘤和5例正常脑组织中P-糖蛋白(Pog]ycoproteln,P-gp)、多药耐药相关蛋白(muhidrug resistance-associated protein,MRP)、肺耐药相关蛋白(lung resistance-related protein,LRP)、DNA拓扑异构酶Ⅱ(topoisomerase Ⅱ,topo Ⅱ)和谷胱甘肽-S-转移酶(glutathione-s-transferase-л,GST-л)5种多药耐药基因蛋白表达强度和分布.结果 P-gp主要表达于毛细血管管壁和管周组织,而在肿瘤细胞表达较低.其他4种多药耐药基因蛋白在毛细血管管壁不表达.结论P-gp在血脑屏障中的神经胶质细胞终足部分参与了对化疗药物的阻滞.增加了颅内肿瘤的耐药性.     

Elevated neonatal salivary anti-casein immunoglobulin A antibodies as an indicator of atopic risk

Elevation of salivary SIgA-anti-casein has been shown to occur in newborn infants at risk of allergy. The present study was designed to follow 158 infants over 3 years to relate the onset of clinical disease to SIgA levels at birth. Newborn infants were divided into 3 groups according to their risk of allergy: Group I, ( n = 62; no allergy risk); Group II, ( n -30; low allergy risk); Group III ( n = 66; high risk group). The groups were matched for smoking, social background, sex, and dietary habits of the patients. SIgA-anti-casein was determined by a direct ELIS A. During the first year 59 infants developed atopic diseases ( n = 37 of Groups I and II; n = 22 of Group III). After 3 years 37/61 infants of the high risk group had developed allergic symptoms. The frequency of atopic disease correlated with increased salivary antibody titers at birth (p < 0.05). 54% of infants with antibody titers > 250 EU/ml developed atopic symptoms at 1 year, 76% high risk infants with this titer developed atopic symptoms at 3 years of age. This study provides evidence that elevation of SIgA-anti-casein at birth not only reflects atopic risk as defined by cord blood IgE or family history, but correlates with the actual development of allergic disease during the first 3 years of life.     

脑缺氧缺血后血脑屏障通透性改变及其机制研究进展

血脑屏障(blood brain barrier,BBB)是存在于血液和脑组织之间的屏障系统,可保持中枢神经系统内环境的相对稳定.脑缺氧缺血可导致BBB通透性发生变化.该文综述了BBB结构基础、功能以及脑缺氧缺血损伤时BBB结构和功能改变的范围、时间及其机制.利用这一理论对BBB调控可能在治疗缺氧缺血性脑损伤及中枢神经...