Aspiration pneumonia induces muscle atrophy in the respiratory, skeletal, and swallowing systems.
Aspiration pneumonia induces muscle atrophy in the respiratory, skeletal, and swallowing systems.
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DOI：
10.1002/jcsm.12297
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发表时间：
2018-08
期刊：
影响因子：
--
通讯作者：
Ichinose M
中科院分区：
文献类型：
--
作者：
Komatsu R;Okazaki T;Ebihara S;Kobayashi M;Tsukita Y;Nihei M;Sugiura H;Niu K;Ebihara T;Ichinose M
在老年患者中反复发作吸入性肺炎是常见的，并导致慢性炎症。炎症诱导肌肉产生促炎细胞因子和萎缩。促炎细胞因子通过激活钙蛋白酶和半胱氨酸天冬氨酸氨基转移酶-3诱导肌肉蛋白分解，然后由泛素-蛋白酶体系统进一步降解。自噬是肌肉萎缩的另一种途径。然而，关于吸入性肺炎与肌肉之间的关系，人们知之甚少。至于吞咽肌肉，目前还不清楚它们是否会产生细胞因子。这项研究的主要目的是确定吸入性肺炎是否导致呼吸系统(横隔肌)、骨骼(胫骨前肌，TA)和吞咽(舌头)系统的肌肉萎缩，及其可能的机制。我们采用了小鼠吸入性肺炎模型和老年肺炎患者的计算机断层扫描(CT)。为诱导吸入性肺炎，小鼠每周5天鼻腔接种小剂量胃酶和脂多糖溶液。分离隔膜、TA和舌头，保存总RNA、蛋白质和冰冻切片。实时定量聚合酶链式反应测定促炎症细胞因子、肌肉E3泛素连接酶和自噬相关基因的表达水平。Western印迹分析确定了肌肉蛋白分解途径的激活。冰冻切片确定肌肉萎缩的存在。应用CT扫描评价老年吸入性肺炎患者的肌肉萎缩情况。吸入刺激增加了炎性细胞因子在隔膜、TA和舌中的表达水平。在肌肉蛋白分解途径中，吸入刺激激活了所有被检测的三块肌肉中的caspase-3，而在横隔肌和TA处被激活，但在舌部不被激活。在所有被检查的三块肌肉中都检测到泛素-蛋白酶体系统的激活。吸入刺激激活了TA和舌头的自噬，而在隔膜检测到微弱的或很少的激活。吸入刺激导致横隔膜、TA和舌肌中较小的肌纤维的比例高于对照组，这表明肌肉萎缩。CT扫描清楚显示老年患者吸入性肺炎继发肌肉萎缩。在临床前动物模型和人类患者中，吸入性肺炎导致呼吸系统、骨骼系统和吞咽系统的肌肉萎缩。横隔膜萎缩可能会减弱咳嗽对痰或误吞内容物的影响。骨骼肌萎缩可能导致继发性骨质疏松症。吞咽肌肉萎缩可能会削弱吞咽功能。因此，肌肉萎缩可能成为吸入性肺炎新的治疗靶点。
Repetition of the onset of aspiration pneumonia in aged patients is common and causes chronic inflammation. The inflammation induces proinflammatory cytokine production and atrophy in the muscles. The proinflammatory cytokines induce muscle proteolysis by activating calpains and caspase‐3, followed by further degradation by the ubiquitin‐proteasome system. Autophagy is another pathway of muscle atrophy. However, little is known about the relationship between aspiration pneumonia and muscle. For swallowing muscles, it is not clear whether they produce cytokines. The main objective of this study was to determine whether aspiration pneumonia induces muscle atrophy in the respiratory (the diaphragm), skeletal (the tibialis anterior, TA), and swallowing (the tongue) systems, and their possible mechanisms. We employed a mouse aspiration pneumonia model and computed tomography (CT) scans of aged pneumonia patients. To induce aspiration pneumonia, mice were inoculated with low dose pepsin and lipopolysaccharide solution intra‐nasally 5 days a week. The diaphragm, TA, and tongue were isolated, and total RNA, proteins, and frozen sections were stored. Quantitative real‐time polymerase chain reaction determined the expression levels of proinflammatory cytokines, muscle E3 ubiquitin ligases, and autophagy related genes. Western blot analysis determined the activation of the muscle proteolysis pathway. Frozen sections determined the presence of muscle atrophy. CT scans were used to evaluate the muscle atrophy in aged aspiration pneumonia patients. The aspiration challenge enhanced the expression levels of proinflammatory cytokines in the diaphragm, TA, and tongue. Among muscle proteolysis pathways, the aspiration challenge activated caspase‐3 in all the three muscles examined, whereas calpains were activated in the diaphragm and the TA but not in the tongue. Activation of the ubiquitin‐proteasome system was detected in all the three muscles examined. The aspiration challenge activated autophagy in the TA and the tongue, whereas weak or little activation was detected in the diaphragm. The aspiration challenge resulted in a greater proportion of smaller myofibers than in controls in the diaphragm, TA, and tongue, suggesting muscle atrophy. CT scans clearly showed that aspiration pneumonia was followed by muscle atrophy in aged patients. Aspiration pneumonia induced muscle atrophy in the respiratory, skeletal, and swallowing systems in a preclinical animal model and in human patients. Diaphragmatic atrophy may weaken the force of cough to expectorate sputum or mis‐swallowed contents. Skeletal muscle atrophy may cause secondary sarcopenia. The atrophy of swallowing muscles may weaken the swallowing function. Thus, muscle atrophy could become a new therapeutic target of aspiration pneumonia.
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DOI：
10.1002/jcsm.12232
发表时间：
2017-12
期刊：
Journal of cachexia, sarcopenia and muscle
影响因子：
--
作者：
Brown JL;Rosa-Caldwell ME;Lee DE;Blackwell TA;Brown LA;Perry RA;Haynie WS;Hardee JP;Carson JA;Wiggs MP;Washington TA;Greene NP
通讯作者：
Greene NP
DOI：
10.1046/j.1365-2389.2003.51318.x
发表时间：
2003-07-01
影响因子：
6.3
作者：
Loeb, MB;Becker, M;Walker-Dilks, C
通讯作者：
Walker-Dilks, C
影响因子：
8.9
作者：
Martone, Anna Maria;Bianchi, Lara;Landi, Francesco
通讯作者：
Landi, Francesco
短期间歇性缺氧后，小鼠隔膜的自噬相关萎缩和代谢重塑。
影响因子：
3.7
作者：
Giordano C;Lemaire C;Li T;Kimoff RJ;Petrof BJ
通讯作者：
Petrof BJ
DOI：
10.1002/jcsm.12222
发表时间：
2017-12
期刊：
Journal of cachexia, sarcopenia and muscle
影响因子：
--
作者：
Cid-Díaz T;Santos-Zas I;González-Sánchez J;Gurriarán-Rodríguez U;Mosteiro CS;Casabiell X;García-Caballero T;Mouly V;Pazos Y;Camiña JP
通讯作者：
Camiña JP