Lu Xiaofang, Wang Yuefen, Liu Chunyan, Wang Yangang
Digestive Disease Center, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing, China.
Department of Nephropathy, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing, China.
PLoS One. 2017 Feb 17;12(2):e0172339. doi: 10.1371/journal.pone.0172339. eCollection 2017.
In this study, we investigated the relationship between tryptophan-5-hydroxytryptamine metabolism, depressive disorder, and gastrointestinal dysfunction in rats after myocardial infarction. Our goal was to elucidate the physiopathologic bases of somatic/psychiatric depression symptoms after myocardial infarction. A myocardial infarction model was established by permanent occlusion of the left anterior descending coronary artery. Depression-like behavior was evaluated using the sucrose preference test, open field test, and forced swim test. Gastric retention and intestinal transit were detected using the carbon powder labeling method. Immunohistochemical staining was used to detect indoleamine 2,3-dioxygenase expression in the hippocampus and ileum. High-performance liquid chromatography with fluorescence and ultraviolet detection determined the levels of 5-hydroxytryptamine, its precursor tryptophan, and its metabolite 5-hydroxyindoleacetic acid in the hippocampus, distal ileum, and peripheral blood. All data were analyzed using one-way analyses of variance. Three weeks after arterial occlusion, rats in the model group began to exhibit depression-like symptoms. For example, the rate of sucrose consumption was reduced, the total and central distance traveled in the open field test were reduced, and immobility time was increased, while swimming, struggling and latency to immobility were decreased in the forced swim test. Moreover, the gastric retention rate and gastrointestinal transit rate were increased in the model group. Expression of indoleamine 2,3-dioxygenase was increased in the hippocampus and ileum, whereas 5-hydroxytryptamine metabolism was decreased, resulting in lower 5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels in the hippocampus and higher levels in the ileum. Depressive disorder and gastrointestinal dysfunction after myocardial infarction involve abnormal tryptophan-5-hydroxytryptamine metabolism, which may explain the somatic, cognitive, and psychiatric symptoms of depression commonly observed after myocardial infarction. Peripheral 5-hydroxytryptamine is an important substance in the gut-brain axis, and its abnormal metabolism is a critical finding after myocardial infarct.
在本研究中,我们调查了心肌梗死后大鼠色氨酸 - 5 - 羟色胺代谢、抑郁症和胃肠功能障碍之间的关系。我们的目标是阐明心肌梗死后躯体/精神抑郁症状的生理病理基础。通过永久性结扎左冠状动脉前降支建立心肌梗死模型。使用蔗糖偏好试验、旷场试验和强迫游泳试验评估抑郁样行为。采用碳粉标记法检测胃潴留和肠道转运情况。免疫组织化学染色用于检测海马体和回肠中吲哚胺2,3 - 双加氧酶的表达。采用带荧光和紫外检测的高效液相色谱法测定海马体、回肠末端和外周血中5 - 羟色胺、其前体色氨酸及其代谢产物5 - 羟吲哚乙酸的水平。所有数据采用单因素方差分析。动脉闭塞三周后,模型组大鼠开始出现抑郁样症状。例如,蔗糖消耗率降低,旷场试验中行进的总距离和中心距离减少,不动时间增加,而在强迫游泳试验中游泳、挣扎和不动潜伏期减少。此外,模型组胃潴留率和胃肠转运率增加。海马体和回肠中吲哚胺2,3 - 双加氧酶的表达增加,而5 - 羟色胺代谢降低,导致海马体中5 - 羟色胺和5 - 羟吲哚乙酸水平降低,回肠中水平升高。心肌梗死后的抑郁症和胃肠功能障碍涉及色氨酸 - 5 - 羟色胺代谢异常,这可能解释了心肌梗死后常见的抑郁躯体、认知和精神症状。外周5 - 羟色胺是肠 - 脑轴中的重要物质,其代谢异常是心肌梗死后的关键发现。