[关键词]
[摘要]
目的:利用GC-MS 代谢组学技术研究低压缺氧环境对大鼠机体代谢的影响,同时评价藏药三果汤散的干预作用。方法:将25 只大鼠随机分为平原对照组、高原模型组、红景天胶囊(诺迪康胶囊)组、三果汤散高剂量组及三果汤散低剂量组,每组5 只,适应1 周后,将模型组和给药组置于5000 m 高原环境模拟舱中,缺氧40 天(22 h·d-1),第40 天后,测定大鼠的血常规指标和肺干湿重比,并取大鼠血浆ECF 衍生后,进行GC-MS 分析,采用主成分分析法研究模型组与正常组之间的代谢物差异,评价藏药三果汤散的干预作用。结果:血常规指标和肺干湿重比均有差异;代谢组学研究结果表明,高原模型组和三果汤散高剂量组、三果汤散低剂量组、红景天胶囊组之间可显著区分,三果汤散干预HAPC 大鼠内源性主要标志物为9-己基-十七烷、甘氨酸、N-甲基-N-甲氧基羰基-乙酯及2,4-二叔丁基苯酚。结论:三果汤散对高原红细胞增多症具有干预作用。
[Key word]
[Abstract]
The article was aimed to study the influence of low pressure and hypoxia on rat metabolism and evaluate the intervention effect of San-Guo-Tang-San (SGTS) on high altitude polycythemia (HAPC) rats. A total of 25 rats were divided into the plain control group, high altitude model group, Hong-Jing-Tian capsule (Nuo-Di-Kang capsule) group, high-dose SGTS group and low-dose SGTS group, with 5 rats in each group. After one week adaptation,rats in the model group and the medication groups were put into the hyperbaric chamber for 40 days (22 h/d) to simulate high altitude environment of 5 000 m. In the end of 40th day, the hemorheology and the dry/wet weight ratio of lung of rats were measured. And plasma samples were derivatized with ECF prior to GC-MS instrumental analysis.Principal component analysis (PCA) was used to find potential biomarkers, and evaluate the intervention effects of SGTS. The results showed that the low pressure and hypoxia changed the hemorheology and dry/wet weight ratio of lung of rats markedly. Metabolomics studies showed that the high altitude model group, high-dose SGTS group, lowdose SGTS group, and Hong-Jing-Tian capsule group can be obviously differentiated. Main markers such as 9-hexylheptadecane, glycine, N-methyl-N-methoxycarbonyl-ethyl ester, 2,4-Di-tert-butylphenol, were found to be the endogenous substances of SGTS which intervening the HAPC rats. It was concluded that SGTS can intervene low pressure and hypoxia induced HAPC.
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[基金项目]
国家自然科学基金委面上项目(30973957):HAPC 藏医多血症的生物学基础及藏药三果汤散干预研究,负责人:张艺;四川省教育厅科研项目(12ZB030):基于体内代谢动态过程的藏药三果汤配伍机理的研究,负责人:邝婷婷;四川省教育厅省属高校科研创新团队建设计划(11TD004):特色中藏药资源的创新研究与开发团队,负责人:张艺。