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地塞米松和岩白菜素对慢性支气管炎的比较作用及其基于核磁共振代谢组学的抗炎机制

Comparative effects of dexamethasone and bergenin on chronic bronchitis and their anti-inflammatory mechanisms based on NMR metabolomics.

作者信息

Ren Xiaolei, Ma Shuangshuang, Wang Juan, Tian Simin, Fu Xiaorui, Liu Xinfeng, Li Zhongfeng, Zhao Baosheng, Wang Xueyong

机构信息

School of Chinese Materia Medica, Beijing University of Chinese Medicine, No. 6, WangJing ZhongHuan South Street, Chao-Yang District, Beijing 100102, China.

Department of Chemistry, Capital Normal University, Beijing 100048, China.

出版信息

Mol Biosyst. 2016 May 24;12(6):1938-47. doi: 10.1039/c6mb00041j.

Abstract

In order to compare the effect of dexamethasone and bergenin on chronic bronchitis and to reveal their anti-inflammatory mechanisms, (1)H NMR-based metabolomics was performed to explore the potential biomarkers of the disease and study the therapeutic mechanisms of the drugs. In this study, 40 Sprague-Dawley male rats were randomly divided into 4 groups, namely control, model, dexamethasone and bergenin groups, with 10 rats in each group. Except for the control group, rats from the other three groups were exposed to tobacco smoke for 1 h d(-1) for 28 days. During the modeling, dexamethasone (0.2 mg kg(-1)) and bergenin (87 mg kg(-1)) were administered orally to dexamethasone or bergenin rats 3 h after exposure every day. On the other hand, control and model rats were intragastrically administered water. According to the results of morphometric analysis of the airway epithelium and the count of white blood cells in the bronchoalveolar lavage fluid (BALF), dexamethasone and bergenin could suppress the infiltration of inflammatory cells, inhibit the secretion of mucus, and reduce white blood cells in BALF. Serum samples from the rats' orbits were collected every week. The metabolic profiles of sera were analyzed by multivariate statistical analyses, including PCA, PLS-DA and OPLS-DA models, and 18 metabolites were identified. The dynamic fluctuations of these biomarkers in sera from different groups were detected. The results suggested that the anti-inflammatory mechanism of dexamethasone may be associated with BCAA metabolism and glycolysis while bergenin could change BCAA metabolism, glycine, serine and threonine metabolism, and glycolysis to treat chronic bronchitis.

摘要

为了比较地塞米松和岩白菜素对慢性支气管炎的疗效并揭示其抗炎机制,采用基于氢核磁共振(¹H NMR)的代谢组学技术来探索该疾病的潜在生物标志物并研究药物的治疗机制。本研究将40只雄性Sprague-Dawley大鼠随机分为4组,即对照组、模型组、地塞米松组和岩白菜素组,每组10只。除对照组外,其他三组大鼠每天暴露于香烟烟雾中1小时,持续28天。在造模期间,地塞米松组大鼠和岩白菜素组大鼠每天在暴露后3小时分别口服地塞米松(0.2 mg·kg⁻¹)和岩白菜素(87 mg·kg⁻¹)。另一方面,对照组和模型组大鼠灌胃给予水。根据气道上皮的形态计量学分析结果和支气管肺泡灌洗液(BALF)中白细胞计数,地塞米松和岩白菜素可抑制炎性细胞浸润,抑制黏液分泌,并减少BALF中的白细胞。每周采集大鼠眼眶血清样本。通过主成分分析(PCA)、偏最小二乘判别分析(PLS-DA)和正交偏最小二乘判别分析(OPLS-DA)模型等多元统计分析方法对血清代谢谱进行分析,鉴定出18种代谢物。检测不同组血清中这些生物标志物的动态波动。结果表明,地塞米松的抗炎机制可能与支链氨基酸代谢和糖酵解有关,而岩白菜素可通过改变支链氨基酸代谢、甘氨酸、丝氨酸和苏氨酸代谢以及糖酵解来治疗慢性支气管炎。

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