达菲干预肾阳虚外感小鼠的血清代谢组学研究

Study of serum metabolomics in tamiflu intervention kidney-yang deficiency syndrome mouse model infected with influenza virus A

目的:通过血清代谢组学的方法,采用LC-MS技术,在正负离子模式下,研究达菲对肾阳虚外感小鼠的干预作用,初步探索达菲在流感治疗过程中调控的代谢通路。方法:36只昆明小鼠随机分为正常组、模型组、达菲组,腹腔注射苯甲酸雌二醇方法复制肾阳虚小鼠模型,然后通过滴鼻感染方法建立病证结合的肾阳虚小鼠外感模型,达菲组以9.75 mg·kg^(-1)·d^(-1)剂量给药干预,每天1次,连续6 d,其他组给予等量的生理盐水;末次给药24 h后取小鼠血清,并进行原始数据采集和相关统计学分析。结果:达菲组小鼠体质量、肛温相对于模型组均有回升趋势;血清样品经过数据分析,最终鉴定了22个存在显著性差异的生物标志物,正离子模式下8个,负离子模式下14个,包括氨基酸类、甘油磷脂类、激素类以及花生四烯酸等物质,以上物质经达菲干预后均出现不同程度的回调。结论:达菲对肾阳虚外感小鼠具有一定干预作用,在干预过程中对甘油磷脂代谢、视黄醇代谢、能量代谢等途径具有一定的调控作用。

Objective:To study the intervention effect of tamiflu on kidney-yang deficiency syndrome mouse model infected with influenza virus A by LC-MS technique in positive and negative ion mode based on serum metabolomics study and explore the metabolic pathways regulated by tamiflu in the course of influenza treatment.Methods:36 Kunming mice were randomly divided into normal group,model group,and tamiflu group.The kidney-yang deficiency syndrome mouse model was established by intraperitoneal injection of estradiol benzoate.The disease-associated kidney-yang deficiency syndrome mouse model was established by nasal infection with influenza virus A.The tamiflu group were intervented with a dose of 9.75 mg·kg^-1·d^-1,once a day for 6 days,other two groups were given the same amount of saline.Serum samples were collected from each mouse of the three groups 24 h after the last administration,and the LC-MS original data were collected and statistical analysis were performed.Results:Compared with the model group,the body weights and rectal temperature of the tamiflu group tended to increase.Twenty-two biomarkers with significant difference were identified in the serum samples.Eight of them were in positive ion mode and fourteen were in negative ion mode.Levels of the substances such as amino acids,glycerophospholipid,hormones and arachidonic acid were regulated with tamiflu intervention.Conclusion:Tamiflu has an intervention effect on kidney-yang deficiency syndrome mouse model infected with influenza virus A and has regulatory effect on glycerophospholipid metabolism,retinol metabolism,energy metabolism during the intervention.