摘要
目的基于代谢组学技术对清开灵软胶囊的解热作用进行评价,探讨与其相关的作用机制。方法采用随机数字表法将18只SD雄性大鼠分为对照组、模型组和给药组,每组6只。模型组和给药组采用干酵母造模;给药组给予清开灵软胶囊内容物的0.5%羧甲基纤维素钠混悬液,以黄芩苷计12.5 mg/kg;模型组和对照组等体积灌胃0.5%羧甲基纤维素钠。应用超高效液相色谱-线性离子阱/静电场轨道阱结合高分辨质谱法(UPLC-LTQ/Orbitrap-MS)的代谢组学技术,在正、负离子模式下对大鼠血浆进行代谢轮廓分析。借助多元变量统计分析对各组数据进行比较分析,寻找血浆中与发热相关的潜在生物标志物,探究清开灵软胶囊对这些内源性成分的逆向调节作用,推断其可能的代谢通路。结果在主成分分析(PCA)图上,对照组、模型组和给药组血浆代谢物谱明显分离,发现并鉴定出8种潜在的血浆生物标志物,分别为乳酸、烟酸、3-呋喃甲酸、琥珀酸、磷脂酰胆碱、花生四烯酸、LysoPE[0∶0/22∶4(7Z,10Z,13Z,16Z)]、油酸;与对照组比较,模型组大鼠血浆中乳酸(P <0.01)、烟酸(P <0.01)、3-呋喃甲酸(P <0.01)、琥珀酸(P <0.01)含量显著升高,磷脂酰胆碱(P <0.05)、花生四烯酸(P <0.01)、LysoPE[0∶0/22∶4(7Z,10Z,13Z,16Z)](P <0.01)、油酸(P <0.05)含量显著降低。给药组大鼠血浆中8种生物标志物含量均显著回调(P <0.01或P <0.05)。结论代谢组学方法可用于清开灵软胶囊的疗效评价,其可能通过调节体内能量代谢和磷脂类代谢发挥解热作用。
Objective To evaluate the antipyretic effect of Qingkailing Soft Capsules based on metabonomics technology and to explore its related mechanism. Methods A total of 18 SD male rats were randomly divided into control group,model group and administration group, with 6 rats in each group. Model group and administration group were feverished by dry yeast. Rats in the administration group were given 0.5% CMC-Na suspension of Qingkailing Soft Capsules with baicalin as 12.5 mg/kg and model group and blank group were intragastrically administered with 0.5% CMC-Na at the same volume. The metabolic profiles of rat plasma were analyzed under positive and negative ion modes by ultra-performance liquid chromatography-inear ion trap/orbitrap high resolution mass spectrometry(UPLC-LTQ/Orbitrap-MS)metabolomics technique. Through the multivariate statistical analysis method, the data of each group were compared and analyzed, and the potential biomarkers related to fever in plasma were searched. The reverse regulation of Qingkailing Soft Capsules on these endogenous components was explored, and the possible metabolic pathways were inferred. Results On the principal component analysis(PCA) chart, the plasma metabolite profiles of the control group, model group and administration group were separated obviously. Eight potential plasma biomarkers were found and identified, which were lactic acid, nicotinic acid, 3-furoic acid, succinic acid, phosphocholine, arachidonic acid, LysoPE [0∶0/22∶4(7 Z, 10 Z, 13 Z, 16 Z)] and oleic acid. Compared with the control group,the contents of lactic acid(P < 0.01), nicotinic acid(P < 0.01), 3-furoic acid(P < 0.05), succinic acid(P < 0.01) were increased significantly, while the contents of phosphocholine(P < 0.05), arachidonic acid(P < 0.01), LysoPE [0∶0/22∶4(7 Z, 10 Z, 13 Z, 16 Z)](P < 0.01), oleic acid(P < 0.05) were decreased significantly, which were in the model group. The contents of eight biomarkers in plasma of rats in the administration group were significantly reversed(P < 0.05 or P <0.01). Conclusion Metabonomics can be used to evaluate the efficacy of Qingkailing Soft Capsules, which may play an antipyretic role by regulating energy metabolism and phospholipid metabolism.
作者
郑蕊
杜守颖
刘宇
郭瑞
ZHENG Rui;DU Shouying;LIU Yu;GUO Rui(Traditional Chinese Pharmacy, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China;Laboratory of Traditional Chinese Medicine Preparation, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China;Traditional Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100029, China;Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100029, China)
出处
《中国医药导报》
CAS
2019年第19期34-38,共5页
China Medical Herald
基金
北京市科技新星计划(xx2015A048)
