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炎症:一种高度保守的、两面神似的现象——从胃肠病学家的视角观察。

Inflammation: a highly conserved, Janus-like phenomenon-a gastroenterologist' perspective.

机构信息

Department of Medical Sciences, Division of Gastroenterology, University of Torino, C.so Bramante 88, 10126, Turin, Italy.

Department of General and Specialist Medicine, Gastroenterologia-U, Molinette Hospital, Turin, Italy.

出版信息

J Mol Med (Berl). 2018 Sep;96(9):861-871. doi: 10.1007/s00109-018-1668-z. Epub 2018 Jul 9.

Abstract

Inflammation is the result of the loss of host's resilience towards the surrounding world. At gross tissue level, inflammation coincides with fluid leakage from vessels, swelling, and blood stasis and extravasation of mononuclear/macrophage cells. Biochemically, these events lead to anoxia and dramatic changes: interruption of the mitochondrial oxidative phosphorylation, influx of the M1 macrophage subset, which live on anaerobic glycolysis. Fall of ATP then leads to energy shortage and debt. In their chronic forms, these phenomena are now known to mark a number of degenerative disorders that have invaded the Western World since the last century: Parkinson's disease, Alzheimer's syndromes, rheumatic diseases, metabolic diseases. Intriguingly, these affections seem to derive from the gut, along two possible pathways. A sort of ascending loss of function caused by accumulation of (and hyperreactivity to) proteins released to restrain spread of enteric viruses: the alpha-synucleins, now increasingly spotted in relation to Parkinson's pathogenesis. The second pathway would entail the intellectual decline perhaps brought about by large use of food containing the proteins of red processed meat. The bacterium Bilophila wadsworthia, thriving in this meat, can erode the mucus layer on colon surfaces, allowing further bacterial flora to approach lining cells, so upgrading the alarm state. We discuss two strategies to prevent such instability from ending up to full-blown inflammatory bowel disease: physical exercise and systematic switch to fibre-containing diets.

摘要

炎症是宿主对周围世界失去弹性的结果。在大体组织水平上,炎症与血管漏液、肿胀、血液淤滞和单核/巨噬细胞外渗同时发生。从生化角度来看,这些事件会导致缺氧和剧烈变化:线粒体氧化磷酸化中断,M1 巨噬细胞亚群的流入,这些细胞依靠无氧糖酵解生存。然后,ATP 的下降导致能量短缺和债务。如今,人们已经知道,这些现象以慢性形式标志着自上个世纪以来侵袭西方世界的许多退行性疾病:帕金森病、阿尔茨海默病综合征、风湿性疾病、代谢性疾病。有趣的是,这些疾病似乎起源于肠道,沿着两种可能的途径发展。一种是由于积累(和对)限制肠道病毒扩散的蛋白质的超反应性而导致的功能逐渐丧失:α-突触核蛋白,现在与帕金森病的发病机制越来越相关。第二种途径可能涉及到由于大量食用含有红色加工肉类蛋白质的食物而导致的智力下降。在这种肉类中大量繁殖的 Bilophila wadsworthia 细菌可以侵蚀结肠表面的黏液层,使更多的细菌菌群接近衬里细胞,从而升级警报状态。我们讨论了两种策略来防止这种不稳定性最终发展为炎症性肠病:体育锻炼和系统地切换到含纤维的饮食。

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