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基于氢谱和 MS 的非靶向代谢组学分析研究四君子汤对丝裂霉素 C 诱导的大鼠免疫毒性的预防作用。

Investigation of the preventive effect of Sijunzi decoction on mitomycin C-induced immunotoxicity in rats by H NMR and MS-based untargeted metabolomic analysis.

机构信息

School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, China.

School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, China.

出版信息

J Ethnopharmacol. 2018 Jan 10;210:179-191. doi: 10.1016/j.jep.2017.08.021. Epub 2017 Sep 1.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Sijunzi decoction (SJZD) is a well known traditional Chinese prescription used for the treatment of gastrointestinal disorders and immunity enhancement. It has been found to indeed improve life quality of chemotherapy patients and extensive used in clinical conbined with chemotherapeutics for the treatment of cancer.

AIM OF THE STUDY

The aim of this study was to investigate the preventive effect of the immunotoxicity of SJZD on mitomycin C (MMC) and the metabolic mechanism of action.

MATERIALS AND METHODS

NMR and MS-based metabolomics approaches were combined for monitoring MMC-induced immunotoxicity and the protective effect of SJZD. Body weight change and mortality, histopathological observations and relative viscera weight determinations of spleen and thymus, sternum micronucleus assay and hematological analysis were used to confirm the immunotoxicity and attenuation effects. An OPLS-DA approach was used to screen potential biomarkers of immunotoxicity and the MetaboAnalyst and KEGG PATHWAY Database were used to investigate the metabolic pathways.

RESULTS

8 biomarkers in plasma samples, 19 in urine samples and 10 in spleen samples were identified as being primarily involved in amino acid metabolism, carbohydrate metabolism and lipid metabolism. The most critical pathway was alanine, aspartate and glutamate metabolism.

CONCLUSIONS

The variations in biomarkers revealed the preventive effect of the immunotoxicity of SJZD on MMC and significant for speculating the possible metabolic mechanism.

摘要

民族药理学相关性

四君子汤(SJZD)是一种著名的中药方剂,用于治疗胃肠道疾病和增强免疫力。已经发现它确实可以提高化疗患者的生活质量,并在临床中广泛应用于与化疗联合治疗癌症。

研究目的

本研究旨在探讨 SJZD 对丝裂霉素 C(MMC)的免疫毒性的预防作用及其代谢作用机制。

材料与方法

采用基于 NMR 和 MS 的代谢组学方法监测 MMC 诱导的免疫毒性和 SJZD 的保护作用。体重变化和死亡率、组织病理学观察和脾、胸腺相对脏器重量测定、胸骨微核试验和血液学分析用于确认免疫毒性和衰减作用。采用 OPLS-DA 方法筛选潜在的免疫毒性生物标志物,并使用 MetaboAnalyst 和 KEGG PATHWAY 数据库研究代谢途径。

结果

在血浆样本中鉴定出 8 种生物标志物,在尿液样本中鉴定出 19 种生物标志物,在脾脏样本中鉴定出 10 种生物标志物,这些生物标志物主要涉及氨基酸代谢、碳水化合物代谢和脂质代谢。最关键的途径是丙氨酸、天冬氨酸和谷氨酸代谢。

结论

生物标志物的变化揭示了 SJZD 对 MMC 的免疫毒性的预防作用,并对推测可能的代谢机制具有重要意义。

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