11.药物和食物因素对胃屏障的影响
胃部的屏障作用时刻保护着胃部免受各种有害物质的侵袭。胃部的本身结构和其所分泌的各种物质能够帮助胃屏障实现这项功能。多种疾病的的发生和胃部的屏障作用损伤有关。
Best Pract Res Clin Gastroenterol. 2014 Dec;28(6):981-94. doi: 10.1016/j.bpg.2014.09.001. Epub 2014 Sep 22.
Pharmacological and alimentary alteration of the gastric barrier.
Author information
Abstract
The gastric barrier contains several lines of defence which protect the epithelium from harmful microbes and toxins. Pre-mucosal defence mechanisms include secreted acid (HCl 0.1 mmol/L) and pepsin, which are capable of denaturing tissue. A tightly adherent mucous layer provides the next line of defence, and physically separates any potentially hazardous substance in the lumen from the mucosal surface. Apical secretion of HCO3(-) maintains a non-acidic microenvironment at the mucosal surface. Membrane-bound phospholipids repel soluble toxins, and sulphydryls scavenge reactive oxygen species. However, when noxious agents overwhelm these mechanisms, the epithelium is damaged. Herein, we discuss the pathological and physiological basis for several disease states which are associated with a breakdown in one or more components of the gastric barrier, including: Helicobacter pylori-associated gastritis, atrophic gastritis, stress-related mucosal disease, age-related gastropathy and portal hypertensive gastropathy. The effect of non-steroidal anti-inflammatory drugs and proton pump inhibitors on the gastric mucosa, is explored. Finally, we outline the alterations in mucosal defence caused by alcohol, caffeine, minerals and vitamins.
Copyright © 2014. Published by Elsevier Ltd.
KEYWORDS:
Atrophic gastritis; Gastric barrier; Helicobacter pylori; MUC; Mucin; Mucosal defence; Non-steroidal anti-inflammatory drugs; Nutrient; Proton pump inhibitor
12. 脑胃轴
胃部对各种不同的固体或液体食物有不同的处理方式，这种不同的处理方式需要依赖大脑的调节。胃部的各种功能一方面受大脑的调节另一方面又收集不同的刺激对大脑进行反馈。目前研究显示幽门螺杆菌对摄食和情绪等脑部功能有影响，但其他在胃部的微生物的作用却还是未知。总而言之，胃脑之间的联系和相互作用十分重要，但还有待于进一步的深入研究和探索，这些研究可能可以为肥胖和功能性胃肠病等的治疗开辟新的路径。
Best Pract Res Clin Gastroenterol. 2014 Dec;28(6):967-79. doi: 10.1016/j.bpg.2014.10.001. Epub 2014 Oct 8.
The stomach-brain axis.
Holtmann G1, Talley NJ2.
Abstract
The stomach has distinct functions in relation to the ingestion and handling of solids and liquids. These functions include storage of the food before it is gradually emptied into the duodenum, mechanical crushing of larger food particles to increase the surface area, secretion of an acidic enzyme rich gastric juice and mixing the ingested food with the gastric juice. In addition, the stomach 'senses' the composition of the gastric content and this information is passed via the vagal nerve to the lateral hypothalamus and the limbic system, most likely as palatability signals that influence eating behaviour. Other sensory qualities related to the stimulation of gastric tension receptors are satiety and fullness. Receptors that respond to macronutrient content or gastric wall tension influence appetite and meal related hormone responses. The ingestion of food - in contrast to an infusion of nutrients into the stomach - has distinct effects on the activation of specific brain regions. Brain areas such as thalamus, amygdala, putamen and praecuneus are activated by the ingestion of food. Gastric nutrient infusion evokes greater activation in the hippocampus and anterior cingulate. The brain integrates these interrelated neural and hormonal signals arising from the stomach as well as visual, olfactory and anticipatory stimuli that ultimately influence eating and other behavioural patterns. Furthermore, there is now good evidence from experimental studies that gastric afferents influence mood, and animal studies point towards the possibility that gastric dysfunction may be a risk factor for mood disorders such as anxiety and depression. The stomach is also not only colonised by Helicobacter pylori but a large array of bacteria. While there is sufficient evidence to suggest that H. pylori may alter caloric intake and mood, the role of other gastric microbiome for the brain function is unknown. To address this appropriate targeted gastric microbiome studies would be required instead of widely utilised opportunistic stool microbiome studies. In summary, it is now well established that there are important links between the brain and the stomach that have significant effects on gastric function. However, the stomach also influences the brain. Disturbances in the crosstalk between the stomach and the brain may manifest as functional GI disorders while disturbances in the stomach-brain communication may also result in an altered regulation of satiety and as a consequence may affect eating behaviour and mood. These observations may enable the identification of novel therapies targeted at the gastroduodenum that positively alter brain function and treat or prevent conditions such as obesity or functional gastrointestinal disorders.
Copyright © 2014. Published by Elsevier Ltd.
KEYWORDS:
Brain-gut interactions; Functional gastrointestinal disorders; Inflammation; Microbiome; Stomach; Stress
13. 胃酸分泌：一个世纪以来的变化
在过去的一个世纪里胃生理科学的进步和发展是进几十年来最让人兴奋的事。进入21世纪后，胃相关疾病的流行病学发生了很多变化，如幽门螺杆菌感染率和胃癌发生率的降低、胃食管反流病及与其相关的质子泵抑制剂应用的增加。
Best Pract Res Clin Gastroenterol. 2014 Dec;28(6):953-65. doi: 10.1016/j.bpg.2014.10.006. Epub 2014 Oct 30.
Gastric acid secretion: changes during a century.
Di Mario F1, Goni E2.
Author information
Abstract
The advances in knowledge of gastric physiology within the past century have been the most exciting and important in this area of interest for many decades. The aim of this presentation consists of a comprehensive review of the extensive recent literature on this topic in order to highlight milestones in the field of gastric physiology, in particular in gastric acid secretion, gastric pathophysiology, acid-related diseases and use of acid regulatory drugs. Moreover, in the 21st century there have been many epidemiologic changes as well as a decrease of Helicobacter pylori infection and gastric cancer together with an increase of gastroesophageal reflux disease and the related increase of pomp proton inhibitor wide use.
Copyright © 2014 Elsevier Ltd. All rights reserved.
KEYWORDS:
Acid regulatory drugs; Chronic atrophic gastritis; Dyspepsia; GERD; Gastric acid secretion; Gastric cancer risk; Gastric physiology; Helicobacter pylori infection; Peptic ulcer disease
14..幽门螺杆菌所产生的具有抗菌性的多肽HPA3NT3对丙酸菌属所致的皮肤座疮的抑制和抗炎作用。
Br J Dermatol. 2014 Dec;171(6):1358-67. doi: 10.1111/bjd.13480. Epub 2014 Nov 9.
Inhibitory and anti-inflammatory effects of the Helicobacter pylori-derived antimicrobial peptide HPA3NT3 against Propionibacterium acnes in the skin.
Ryu S1, Park Y, Kim B, Cho SM, Lee J, Lee HH, Gurley C, Song K, Johnson A, Armstrong CA, Song PI.
Author information
Abstract
BACKGROUND:
An effective treatment strategy for acne vulgaris is the reduction of Propionibacterium acnes in the skin. The Helicobacter pylori-derived synthetic antimicrobial peptide HPA3NT3 is a customized α-helical cationic peptide with antibacterial and anti-inflammatory activity.
OBJECTIVES:
To examine the role of HPA3NT3 as a treatment against P. acnes-induced skin inflammation.
METHODS:
Morphological alteration of individual P. acnes cells by HPA3NT3 was visualized by scanning electron microscopy. Modulation by HPA3NT3 of a number of P. acnes-induced innate immune responses was analysed in vitro using cultured normal human keratinocytes (HKs), and in vivo using the ICR mouse, a well-established model for P. acnes-induced skin inflammation.
RESULTS:
The minimum inhibitory concentration of HPA3NT3 against P. acnes was low (0·4 μmol L(-1) ). HPA3NT3 showed no cytotoxicity to HK cells at the concentrations used in our in vitro and in vivo studies. Treatment with HPA3NT3 in vitro induced morphological disruptions in P. acnes cells suggestive of a bactericidal effect. HPA3NT3 significantly decreased P. acnes-induced interleukin-8 expression and intracellular calcium mobilization in HK cells by inhibiting P. acnes-activated Toll-like receptor 2-mediated nuclear factor-κB signalling pathways. Intradermal injection of HPA3NT3 in vivo effectively decreased viable P. acnes, as well as erythema, swelling and inflammatory-cell infiltration in ICR mouse ears inoculated with P. acnes.
CONCLUSIONS:
Our data suggest that HPA3NT3 has potential as a therapeutic agent for acne vulgaris due to its antimicrobial effects on P. acnes and its ability to block P. acnes-induced inflammation.
© 2014 British Association of Dermatologists.
15.幽门螺杆菌γ-谷酰基转氨基通过PLC-IP3受体在AGS细胞释放产生Ca(2 +)。
前期研究显示从幽门螺杆菌分离出的GGT导致了AGS细胞的凋亡。本文我们将研究Ca(2 +)对GGT导致了AFS细胞的凋亡的作用。结果显示Ca(2 +)对GGT导致了AGS细胞的凋亡具有明显作用。
Can J Microbiol. 2014 Dec;60(12):865-8. doi: 10.1139/cjm-2014-0464.
Helicobacter pylori γ-glutamyl transpeptidase-induced Ca(2+) release via PLC-IP3 receptors in AGS cells.
Park EH1, Kim JM, Kim KM, Kang D, Cho YA, Choi JY, Song JY, Kang HL, Lee WK, Cho MJ, Rhee KH, Seo JH, Youn HS, Baik SC.
Author information
Abstract
In our previous study, γ-glutamyl transpeptidase (GGT) isolated from Helicobacter pylori induced apoptosis of AGS cells. Here, we investigate Ca(2+) effects on GGT-induced apoptosis. The GGT transiently and significantly increased intracellular Ca(2+) concentration ([Ca(2+)]i) in AGS cells in a dose-dependent manner (P < 0.05). The GGT-induced Ca(2+) increase resulted from Ca(2+) influx and release through the phospholipase C - inositol 1,4,5-trisphosphate (PLC-IP3) pathway. The GGT-induced apoptosis was significantly reduced by treatment with U73122 (a PLC inhibitor) and xestospongin (an IP3 receptor antagonist) (P < 0.05). These results indicate that GGT could induce apoptosis of AGS cells by high levels of [Ca(2+)]i.
KEYWORDS:
Helicobacter pylori; apoptose; apoptosis; calcium; γ-glutamyl transpeptidase
16. 小鼠模型显示早期或晚期使用抗生素干预均有利于阻碍幽门螺杆菌相关胃癌发生
幽门螺杆菌感染与各种消化道疾病和胃癌的发生相关。研究发现幽门螺杆菌感染的WT小鼠没有发生相关癌症，但是缺乏抑癌基因P27的小鼠发生了胃癌，本研究应用p27缺失小鼠，使其幽门螺杆菌感染，以感染后15周为临界分为早期和晚期给予奥美拉唑，甲硝唑和克拉霉素干预。结果显示早期或晚期使用抗生素干预均有利于对阻碍幽门螺杆菌相关胃癌发生。
Cancer Lett. 2014 Dec 1;355(1):106-12. doi: 10.1016/j.canlet.2014.09.010. Epub 2014 Sep 11.
Early or late antibiotic intervention prevents Helicobacter pylori-induced gastric cancer in a mouse model.
Zhang S1, Lee DS2, Morrissey R3, Aponte-Pieras JR1, Rogers AB4, Moss SF5.
Author information
Abstract
H. pylori infection causes gastritis, peptic ulcers and gastric cancer. Eradicating H. pylori prevents ulcers, but to what extent this prevents cancer remains unknown, especially if given after intestinal metaplasia has developed. H. pylori infected wild-type (WT) mice do not develop cancer, but mice lacking the tumor suppressor p27 do so, thus providing an experimental model of H. pylori-induced cancer. We infected p27-deficient mice with H. pylori strain SS1 at 6-8 weeks of age. Persistently H. pylori-infected WT C57BL/6 mice served as controls. Mice in the eradication arms received antimicrobial therapy (omeprazole, metronidazole and clarithromycin) either "early" (at 15 weeks post infection, WPI) or "late" at 45 WPI. At 70 WPI, mice were euthanized for H. pylori determination, histopathology and cytokine/chemokine expression. Persistently infected mice developed premalignant lesions including high-grade dysplasia, whereas those given antibiotics did not. Histologic activity scores in the eradication groups were similar to each other, and were significantly decreased compared with controls for inflammation, epithelial defects, hyperplasia, metaplasia, atrophy and dysplasia. IP-10 and MIG levels in groups that received antibiotics were significantly lower than controls. There were no significant differences in expression of IFN-γ, TNF-α, IL-1β, RANTES, MCP-1, MIP-1α or MIP-1β among the three groups. Thus, H. pylori eradication given either early or late after infection significantly attenuated gastric inflammation, gastric atrophy, hyperplasia, and dysplasia in the p27-deficient mice model of H. pylori-induced gastric cancer, irrespective of the timing of antibiotic administration. This was associated with reduced expression of IP-10 and MIG.
Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
KEYWORDS:
Chemokines; Gastric cancer; Helicobacter pylori; Inflammation; Mouse model
17.中国人群幽门螺杆菌感染率与体重指数之间的关系
幽门螺杆菌感染与肥胖之间是否存在相关性仍然存在着争议，本研究旨在探讨在中国人群中幽门螺杆菌感染与身体质量指数(BMI)是否存在相关性。通过对3859名幽门螺杆菌感染患者和4967名对照者的分析，结果显示肥胖与幽门螺杆菌感染呈明显正相关性，高体重指数(BMI)会增加幽门螺杆菌感染的风险。
Helicobacter. 2014 Dec;19(6):437-42. doi: 10.1111/hel.12153. Epub 2014 Sep 25.