| 基于UHPLC/Q-TOF MS联用技术的顺铂肾毒性代谢组学研究 |
| 投稿时间：2015-03-31 修订日期：2015-05-28 点此下载全文 |
| 引用本文：夏德萌,卢宏涛,施烜,郝晓伟,高松燕,杨峰,谌卫,董昕.基于UHPLC/Q-TOF MS联用技术的顺铂肾毒性代谢组学研究[J].医学研究杂志,2016,45(1):34-39 |
| DOI：
10.11969/j.issn.1673-548X.2016.01.009 |
| 摘要点击次数: 1527 |
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| 基金项目:国家自然科学基金青年科学基金资助项目(81302732);上海市自然科学基金资助项目(13ZR1450100);第二军医大学创新能力培养计划项目 |
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| 中文摘要:目的 构建顺铂诱导的急性肾损伤小鼠模型,利用代谢组学方法,筛选顺铂诱导急性肾损伤的潜在生物学标志物,进一步探索其可能形成机制。方法 通过对小鼠腹腔注射顺铂溶液,建立急性肾损伤的实验动物模型;利用超高效液相色谱-四极杆飞行时间串联质谱(UHPLC/Q-TOF MS)技术对健康对照组及急性肾损伤模型组的血清进行代谢轮廓分析,通过多元统计分析方法对两组间的数据进行分析,筛选顺铂诱导小鼠急性肾损伤的潜在生物学标志物。结果 主成分分析结果表明,模型组与对照组有明显的分离趋势,显示小鼠血清的内源性代谢物发生了较为显著地变化,进一步分析筛选,得到40种顺铂诱导急性肾损伤的差异代谢物,涉及氨基酸代谢、脂肪代谢、糖类代谢、三羧酸循环等多种代谢途径。结论 应用代谢组学的方法可以初步筛选顺铂诱导急性肾损伤的差异代谢物,并对其涉及的生物通路进行归属,初步探索顺铂肾毒性的形成机制。 |
| 中文关键词:顺铂 代谢组学 急性肾损伤 超高效液相色谱-四极杆飞行时间串联质谱 |
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| Cisplatin Nephrotoxicity Metabolomics Studies Based on UHPLC/Q-TOF MS Technology |
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| Abstract:Objective To build a mouse model of acute kidney injury induced by cisplatin. Then we try to find cisplatin-induced acute kidney injury potentialbiomarkers and explore the possible mechanism of acute kidney injury by using metabolomics methods. Methods We inject cispatin solution to peritoneal of mice toestablish experimental animal models of acute kidney injury.Serum metabolic profiling between the control group and the experimental group was analyzed using ultra-high performance liquid chromatography with tandem quadrupole time of flight mass spectrometer(UHPLC/Q-TOF MS). Multivariate statistical analysis methods was used to analyze the data between the two groups. At last, we select the potential biomarkers of acute kidney injury. Results Principal component analysis showed that separation trend of the experimental group and the control group was significantly. The endogenous substances in mice serum had made a huge change. We got forty potential biomarkers of acute kidney injury after screening, and the main metabolic pathways were amino acid metabolism, fat metabolism, carbohydrate metabolism and Krebs cycle, etc. Conclusion Application of metabolomics approach could select potential biomarkers of cisplatin-induced acute kidney injury and explore the mechanism that cisplatin cause acute kidney injury. |
| keywords:Cisplatin Metabolomics Acute kidney injury UHPLC/Q-TOF MS |
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