肠道和呼吸道菌群与肺部疾病的研究新进展

宿主微生物群落对机体局部以及系统免疫的影响已逐渐引起人们的关注,目前发现局部的微生物群落能够对机体远端部位的免疫能力造成影响。肠道和呼吸道菌群稳态对机体免疫系统发育以及抗病原微生物感染至关重要,肠道和呼吸道菌群失衡与炎症性疾病、代谢性疾病以及过敏性疾病密切相关。肠道和呼吸道菌群失衡会通过"肠—肺轴"的相互作用,引起免疫系统改变与急性、慢性肺部疾病的发生。在这篇综述中,我们对肠道微生物和呼吸道微生物在肠-肺轴中发挥作用的研究进展作一总结,并对从微生物角度进行疾病治疗干预的可能性进行分析。     

微生态失调对“肺-肠”相关疾病作用机制和进展研究

慢性肠道和肺部疾病的发生与进展已被证明与微生态的紊乱和失调相关。肠道微生物改变可能促进肺部感染,肺部疾病也可能影响肠道菌群的组成。而微生物群可通过“肺-肠”轴介导慢性肠道疾病如炎症性肠病与肺部慢性疾病之间的相互作用。本文对微生态在肺和肠相关疾病的“肺-肠”轴相互影响过程中所起的作用,以及相关机制研究进展进行综述。     

肠道菌群与急性肺损伤/急性呼吸窘迫综合征的关系

肠道和肺部具备相似的黏膜结构、生理功能和免疫功能。胃肠道和呼吸道黏膜菌群紊乱影响肠道疾病和急性肺损伤/急性呼吸窘迫综合征(acute lung injury/acute respiratory distress syndrome,ALI/ARDS)发展和预后。当肠道微生物群失调时会导致肠道炎症的发生,诱发肠道免疫反应并增加肠黏膜上皮的通透性,细菌及炎症因子经肠-肺轴或其他路径引发肺部疾病,致使组织器官缺血缺氧,造成肺部疾病预后不良。本文将重点关注肠道菌群失调与ALI/ARDS的关系,阐述肠道菌群失调引发的肠道和肺部慢性炎症,为肠道菌群失调引发肺部疾病的原因及其内在机制的研究提供新思路,为后续治疗提供新的线索。     

肠道菌群在肺纤维化疾病中的调节作用

肺纤维化是一种以成纤维细胞增殖及大量细胞外基质及胶原聚集,并伴随炎症损伤为特征的呼吸系统疾病终末期改变。该疾病以肺功能障碍和呼吸衰竭为主要病理基础,发病率逐年上升,目前治疗方法有限。在肠肺之间的功能调控研究中,肠道菌群构成变化引起的机体微生态失调能够通过多种方式影响呼吸系统疾病的进程。本文聚焦于肺纤维化等肺部疾病的肠肺调控研究前沿领域,综述了多种肺纤维化疾病的致病机制、肠道菌群的功能、肠肺双向调节和益生菌群干预治疗等方面的最新进展。此外,本文也提出了该领域目前存在的问题,以期为今后的调控机制探索和治疗药物研发提供有力的理论支持及策略支撑。     

肠道菌群对慢性阻塞性肺疾病的影响研究

慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)是肺部常见疾病,肺部炎症作为COPD的一贯特征,其炎症反应多为中性粒细胞型。近年的流行病学调查表明,COPD在我国的防治现状并不理想,表现出高致死率、致残率及高隐匿性的特点。目前COPD的有效治疗措施匮乏,寻找新的治疗突破口迫在眉睫。现有的研究显示,肠道菌群及其代谢产物与多种疾病的发生发展有着密切关联,其与肺系疾病的联系称为“肺—肠轴”。在COPD中,这可能是通过改变肠道屏障完整性、产生抗炎性代谢产物和调节骨髓造血免疫功能来实现的。但现有的研究尚不能明确特定的肠道菌群对COPD的作用机制,这也是未来研究的方向及COPD治疗可能的突破口。     

呼吸系统流感病毒感染通过菌群介导的Th17细胞依赖的炎症诱导肠道免疫损伤

<正>流感是一种发生于多种禽类和哺乳动物的感染性呼吸系统疾病。临床上最普遍的症状包括咳嗽、发热和头痛等,同时还经常伴有腹痛、呕吐和腹泻等胃肠道感染样症状。但是为什么主要发生于肺部的流感病毒感染会引起肠道的损伤?其中的机制目前还不清楚。在这篇2014年11月17日发表于《实验医学杂志》(Journal of Experimental Medicine)的文章中,作者使用PR8流感病毒鼻内感染C57小鼠,发现确实存在肺部损伤和肠道损伤,而肝和肾脏组织没有看到明显的病变。为了证明肠道损伤是否是由于     

肠道菌群与腹泻型肠易激综合征 相关性的研究进展

肠易激综合征(IBS)是一种常见的功能性胃肠道疾病,其特征是反复发作的腹痛,伴随排便频率与大便性状的改变。腹泻为主的肠易激综合征(IBS-D)是其主要亚型,主要表现是腹痛和腹泻。目前IBS-D的发病机制尚不完全明确,但大量的研究提示可能与胃肠道动力紊乱、黏膜通透性和肠上皮屏障功能改变、内脏高敏感性增加、"脑-肠-菌"轴失调、肠道感染与炎症反应激活、精神心理因素异常等有关。随着研究的不断深入,发现肠道菌群与IBS-D的关系密切,调节肠道菌群的益生菌干预成为缓解IBS-D相关症状的手段之一。本研究就近十余年来肠道菌群情况与IBS-D关系的研究现状作一综述。     

肺部菌群对过敏性哮喘的影响CSCD

过敏性哮喘是一种常见的过敏性疾病,其发病机制尚未完全清楚,但共生微生物与宿主免疫稳态的建立及维持关系密切。近年来的研究发现肠道菌群在过敏性哮喘的发生发展中起主要作用,“肺-肠轴”概念的提出阐释了肺部菌群与肠道菌群之间的串扰关系。研究证实肺部菌群与过敏性哮喘密切相关,并通过肺-肠轴直接或间接影响过敏性哮喘的发生发展。本文分析肺部菌群与过敏性哮喘的相关性及可能的机制,深入了解肺部菌群在过敏性哮喘中的作用及意义,以期为过敏性哮喘的临床预防及诊疗拓宽思路。     

肠道菌群与病毒性肺炎关系的研究进展

在21世纪头20年里,呼吸道病毒造成的地区性乃至世界性的流行已经发生多次,而疫情的暴发严重威胁人类健康与生存,但临床上,仍缺乏针对病毒的特异性治疗手段。随着肠道微生态相关研究的广泛开展,肠道菌群在哮喘,纤维化及细菌性感染等多种肺部疾病的发病及防治中发挥着重要作用,成为"肠-肺轴"的关键枢纽。病毒性肺炎与肠道微生态间也存在着紧密的相互联系,通过改善肠道菌群,对呼吸病毒感染具有较好的防治作用。其内在机制主要涉及到:通过增强肠道黏膜屏障功能、减少继发性细菌的感染;通过菌体成分或者代谢产物如短链脂肪酸,色氨酸代谢产物等提高固有样淋巴细胞(Innate lymphoid cells,ILC)、单核-巨噬细胞、树突状细胞、自然杀伤细胞(Natural killer,NK)、粒细胞等固有免疫细胞的抗病毒免疫功能及调节Th17/Treg平衡抑制过度的炎症反应等。本文将系统回顾已发表的文章,对肠道菌群在病毒性肺炎方面的研究作系统的阐述,以求为研究者在病毒性肺炎的机制探究和防治方面提供帮助。     

肠道菌群与脑-肠轴相互作用关系研究进展

人体肠道内定植了大量的细菌,它们参与机体多种生理功能的维持。大脑与胃肠道之间通过脑-肠轴进行双向关联。近年研究发现肠道菌群与脑-肠轴可相互作用、相互影响。肠道菌群可影响机体神经内分泌系统及免疫系统的功能,脑-肠轴功能变化同样也会改变肠道的菌群结构。本研究就肠道菌群与脑-肠轴功能相互影响的研究进展作一综述,以期为深入了解肠道菌群对脑-肠轴功能的影响提供参考。     

白蚁与动物及微生物的共生类型及其机制

综述了白蚁螱客的主要种类、共生关系及相关机制的研究进展。白蚁螱客中,已报道的动物种类达170种。在与动物的共生关系中存在偏利共生（宾主共栖和异种共栖）、互利共生和无关共生三种;在与微生物的共生关系中,存在与内生菌（原生动物、细菌、真菌和放线菌）和外生菌（蚁巢伞菌等）间的互利关系。指出了白蚁与螱客研究中存在的问题,给出了解决方案,并提出了今后可能的研究热点或方向,为白蚁的综合利用（如纤维素酶）及今后研究物种间的协同进化提供了基础资料。     

New amino-dithiaphospholanes and phosphoramidodithioites and their rhodium and iridium complexes

New sulfur derivatives of phosphoramidite ligands were synthesized and the impact of the sulfur unit on the spectroscopic properties of their rhodium and iridium complexes was investigated. The new ligands Bn₂NPSCH₂CH₂S^a(P-S^a) (Bn = benzyl, 4), Bn₂NPSCHCHS^a(CH₂)₃C^aH₂(P-S^a)(C^a-S^a) (6) and Bn₂NP(4-XC₆H₄OMe)₂ (X = S, 7a; X = O, 7b) were converted to the rhodium and iridium complexes trans-[Rh(CO)Cl(L)₂] (L = 4, 6, 7), [RhCl(COD)(L)] (L = 4, 6, 7), [IrCl(COD)(7a)] and [IrCl₂Cp∗(6)]. For comparison, some phosphoramidite complexes of these formulations also were synthesized. The new metal complexes were spectroscopically analyzed. For the carbonyl complexes, the ν_CO IR stretching frequencies were lower than for the corresponding phosphite and phosphoramidite ligands. The ¹J_PRh coupling constants for the rhodium complexes with the new ligands were also smaller than for the respective phosphoramidite and phosphite complexes. Finally, the ¹J_PSe coupling constants of the selenides of the new ligands were lower than those of the phosphoramidite ligands but higher than for PPh₃. The spectroscopic data reveal that the new thio ligands 4, 6 and 7a are more electron donating than phosphites and phosphoramidites but less electron donating than PPh₃.     

Astrocytes and Synaptosomes Transport and Metabolize Lactate and Acetate Differently

Astrocytes transport the monocarboxylate acetate, but synaptosomes do not. The reason for this is unknown, because both preparations express monocarboxylate transporters (MCT). The transport and metabolism of lactate, another monocarboxylate, was examined in these two preparations, and the results were compared to those for acetate. Lactate transport is more rapid in astrocytes than in synaptosomes, but of lower affinity (Kms of 17 and 4 mM, respectively). Lactate (0.2 mM) is metabolized to CO2 more rapidly in synaptosomes than in astrocytes (rates of 0.37 and 0.07 nmol x mg protein(-1) x min(-1), respectively). The reason for this is unclear, but cellular differences in lactate dehydrogenase isotype expression may be involved. Acetate is metabolized to CO2 more rapidly in astrocytes than in synaptosomes (rates of 0.43 and 0.02 nmol x mg protein(-1) x min(-1), respectively). This is likely due to cellular differences in the expression of monocarboxylate transporter subtypes.     

Rapporteur report: Basics and technology and metrology and standards

The first and second sessions of the Workshop focussed on the basics of ultrasound and infrasound, their applications in both industry and medicine, and metrology and protection standards for ultrasound applications.     

Relative and combined effects of ethanol and protein deficiency on strontium and barium bone content and fecal and urinary excretion

To elucidate accumulation of minerals in human iliac arteries with aging, the content of minerals was analyzed by inductively coupled plasma atomic emission spectrometry. Bilateral common, internal, and external iliac arteries of 16 men and 8 women, ranging ages from 65 to 93 yr, were examined. It was found that an extremely high accumulation of calcium and phosphorus occurred in the common iliac artery at old age, being higher than that of the internal and external iliac arteries. It should be noted that the accumulation of calcium and phosphorus is the highest in the common iliac artery among the human arteries examined to date. Regarding sexual differences, the content of calcium and phosphorus in the common and internal iliac arteries was higher in women than in men, whereas their content in the external iliac artery was lower in women than in men.     

Prostaglandin and thromboxane production by human and guinea-pig macrophages and leucocytes

The ability of partially purified human and guinea-pig haematogenous cell populations, when cultured in vitro, to metabolise arachidonic acid (AA) has been studied. Supernatants from 24 hour cell culture have been subjected to analysis for products of AA metabolism by gas chromatography with electron-capture detection.The cell types studied were human peripheral blood monocytes (both glass adherent and non-adherent), neutrophils, eosinophils and leukemic leucocytes; thoracic duct lymphocytes and lung alveolar macrophages. From the guinea-pig, induced and non-induced macrophage or neutrophil enriched peritoneal exudate populations, lymph node cells, peritoneal eosinophils and peripheral blood platelets were examined. Supernatants were assayed for the presence of PGE₂, PGD₂, PGF_2α, TXB₂ and 6-keto-PGF_1α. In all types studied PGE₂ and TXB₂ were the major products formed. The identification of PGE₂ and TXB₂ was confirmed by GC/MS with multiple ion monitoring.The results have been compared with other reports and their possible significance discussed in relation to the proposed role of prostaglandins as mediators and modulators in immunopathology.     

Chemokines and cytokines: axis and allies in asthma and allergy

Allergic asthma can be precipitated by many factors. For the atopic person, fungus, pollen, dust mites, cockroach antigens, and diesel exhaust are all agents that may trigger an allergic attack. Cytokines and chemokines are integral mediators of fungal asthma. From the earliest time points, they recruit and activate the cells required for the clearance of fungus as well as being critical factors involved in the immunopathology of this disease. In the final analysis, it is clear that these mediators can act to the benefit or the detriment of the host.     

Oxidation and nitration of ribonuclease and lysozyme by peroxynitrite and myeloperoxidase

In spite of the many studies on protein modifications by reactive species, knowledge about the products resulting from the oxidation of protein-aromatic residues, including protein-derived radicals and their stable products, remains limited. Here, we compared the oxidative modifications promoted by peroxynitrite and myeloperoxidase/hydrogen peroxide/nitrite in two model proteins, ribonuclease (6Tyr) and lysozyme (3Tyr/6Trp). The formation of protein-derived radicals and products was higher at pH 5.4 and 7.4 for myeloperoxidase and peroxynitrite, respectively. The main product was 3-nitro-Tyr for both proteins and oxidants. Lysozyme rendered similar yields of nitro-Trp, particularly when oxidized by peroxynitrite. Hydroxylated and dimerized products of Trp and Tyr were also produced, but in lower yields. Localization of the main modified residues indicates that peroxynitrite decomposes to radicals within the proteins behaving less specifically than myeloperoxidase. Nitrogen dioxide is emphasized as an important protein modifier.