基于代谢组学方法研究麻黄细辛附子汤治疗肾阳虚外感小鼠的作用机制  

Mechanism of Mahuang Xixin Fuzi Decoction on the mice model of kidney-yang deficiency syndrome infected with influenza virus A based on serum metabolomics

作　　者：孙启慧 付业佩 李灿[1] 王旭[1] 蒋海强[1] 杨勇[1] 容蓉[1] 赵渤年[2] SUN Qi-hui;FU Ye-pei;LI Can;WANG Xu;JIANG Hai-qiang;YANG Yong;RONG Rong;ZHAO Bo-nian(Shandong University of Chinese Medicine, Jinan 250355, China;Shandong Academy of Chinese Medicine, Jinan 250014, China)

机构地区：[1]山东中医药大学,济南250355 [2]山东省中医药研究院,济南250014

出　　处：《中华中医药杂志》2018年第5期1752-1757,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81774167);国家科技重大专项(No.2017ZX09101003-003-004);山东省重点研发计划(No.2017CXGC1309)~~

摘　　要：目的:运用代谢组学方法,研究麻黄细辛附子汤(MXF)对肾阳虚外感小鼠血清中内源性物质的调节作用,探讨MXF的药效及作用机制。方法:雄性昆明小鼠随机分组,采用腹腔注射苯甲酸雌二醇方法复制肾阳虚小鼠,然后H1N1滴鼻感染,建立肾阳虚外感小鼠模型;MXF组给药剂量为2.5g·kg-1·d-1,每日1次,连续6d;肾阳虚小鼠于造模第13-15天测定记录体质量、肛温、趾温、游泳时间,肾阳虚外感小鼠每天记录体质量、肛温、死亡率等,于末次给药24h后收集血清样本,取肺、胸腺、肾上腺等计算脏器指数;血清样本采用HPLC-TOF/MS检测。结果:肾阳虚小鼠精神萎靡,体质量、肛温、趾温、游泳时间等显著下降(P<0.05,P<0.01);与模型组比较,MXF组小鼠体质量、肛温都有上升趋势;死亡率为0,肺指数为0.700±0.072,胸腺指数、肾指数、睾丸指数显著升高(P<0.05,P<0.01);血清样本采集的数据经统计分析,最终鉴定出D-葡萄糖、羟脯氨酸、L-乳酸等13种生物标志物,MXF组13种物质均出现不同程度的回调。结论:MXF治疗肾阳虚外感小鼠可能是通过改善糖代谢,调节视黄醇代谢、甘油磷脂代谢等多靶点、多途径发挥药效。Objective： To study the mechanism of Mahuang Xixin Fuzi Decoction（MXF） on mice model of kidney-yang deficiency syndrome infected with influenza virus A by metabolomics method. Methods： KM mice were randomly divided into three groups. The kidney yang deficiency mice were induced by intraperitoneal injection of estradiol benzoate and then infected with Influenza virus A. The dose of MXF was 2.5 g · kg-1 · d-1 and given by gavage for 6 consecutive days after inoculation. The body weight, rectal temperature, toe temperature and swimming time of kidney-yang deficiency mice model were measured and recorded on the 13 th to 15 th. Then body weight, rectal temperature and mortality of kidney-yang deficiency syndrome infected with influenza virus A were recorded daily. The lungs, thymus, adrenal glands and other organs were weighed and the organ index was calculated. Serum samples were collected 24 hours after the last administration for HPLC-TOF-MS analysis. Results： Body weight, rectal temperature, toe temperature, swimming time, etc. significantly decreased of mice with kidney-yang deficiency syndrome（P〈0.05, P〈0.01）. Compared with model group, the body weight and rectal temperature of MXF group were increased, and their mortality rate was zero, lung index was 0.700±0.072, thymus index, renal index and testis index were significantly increased in MXF group（P〈0.05, P〈0.01）. The original data collected from the serum samples were analyzed by statistics, then 13 kinds of endogenous were founded, including D-glucose, hydroxyproline, L-lactic acid and so on. The endogenous recovered to normal levels in MXF group. Conclusion： MXF may play a role in improving glucose metabolism, adjusting retinol metabolism and glycerophospholipid metabolic pathways.

关 键 词：代谢组学 麻黄细辛附子汤 肾阳虚外感 生物标志物 

分 类 号：R285.5[医药卫生—中药学]