基于代谢组学技术的清开灵软胶囊解热作用机制研究
|
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.
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.
引文
[1] He S,Li WS,Luo YJ,et al. Qingkailing Injection for Treatment of Children Pneumonia Induced by Respiratory Syncytial Virus:A Meta-Analysis of Randomized Controlled Trials[J]. Chin J Integr Med,2018,24(4):288-295.
[2]吴春芝,刘红在,岳文,等.清开灵制剂的临床应用研究进展[J].中国药房,2017,28(18):2588-2592.
[3]孙美利,李蕾,张舒媛,等.清开灵制剂药理作用研究现状[J].现代中药研究与实践,2014,28(5):76-78.
[4] Zhang PJ,Li YM,Zhang YN,et al. Application and prospect of toxicity quality markers of Chinese materia medica based on metabolomics[J]. Chin Herbal Med,2018, 2:108-116.
[5]刘海玉.基于代谢组学技术的清开灵注射液解热作用活性成分筛选及机制研究[D].北京:北京中医药大学,2015.
[6]郭明星.清开灵注射液解热作用代谢组学研究[D].北京:北京中医药大学,2014.
[7] Qin L,Zhang Z,Guo M,et al. Plasma metabolomics combined with lipidomics profiling reveals the potential antipyretic mechanisms of Qingkailing injection in a rat model[J].Chem Biol Interact,2016,254:24-33.
[8] Gao X,Guo M,Peng L,et al. UPLC Q-TOF-MS-Based Metabolic Profiling of Urine Reveals the Novel Antipyretic Mechanisms of Qingkailing Injection in a Rat Model of Yeast-Induced Pyrexia[J]. Evid Based Complement Alternat Med,2013:864747.
[9]周耀中,杨涛,季雪峰,等.基于UHPLC/MS的冠心病心绞痛血瘀证患者血清代谢组学研究[J].江西中医药,2018,6(50):25-28.
[10]周永峰,牛明,房吉祥,等.基于UPLC-Q-TOF-MS的五味子保肝作用代谢组学研究[J].中国中药杂志,2018,43(18):3756-3763.
[11]邵卫绪.基于代谢组学的抗心绞痛常见药物的比较[J].中国中医药现代远程教育,2014,12(10):100-102.
[12]郑磊.基于1H-NMR技术的黄连上清丸解热作用代谢组学研究[D].南昌:南昌大学,2014.
[13]杜丽娜.基于UPLC-MS技术的呼吸道合胞病毒肺炎痰热闭肺证代谢模式及金欣口服液干预研究[D].南京:南京中医药大学,2015.
[14]招树涛,甘智涛,黄丽霜.血清salusin-α及脂蛋白相关磷脂酶A2水平与颈动脉粥样硬化不稳定斑块患者并发脑梗死的相关性[J].临床和实验医学杂志,2018,17(11):1170-1172.
[15]王洪志,刘晓阳,于远军,等.缺血性脑血管病患者血清Lp-PLA2、Hcy及hs-CRP与颈动脉病变特点的相关性分析[J].疑难病杂志,2018,17(9):888-891,904.
[16]王晞.血清抗磷脂酶A2受体抗体在膜性肾病诊断中的应用价值[J].中国医药导报,2018,15(3):60-63.
[2]吴春芝,刘红在,岳文,等.清开灵制剂的临床应用研究进展[J].中国药房,2017,28(18):2588-2592.
[3]孙美利,李蕾,张舒媛,等.清开灵制剂药理作用研究现状[J].现代中药研究与实践,2014,28(5):76-78.
[4] Zhang PJ,Li YM,Zhang YN,et al. Application and prospect of toxicity quality markers of Chinese materia medica based on metabolomics[J]. Chin Herbal Med,2018, 2:108-116.
[5]刘海玉.基于代谢组学技术的清开灵注射液解热作用活性成分筛选及机制研究[D].北京:北京中医药大学,2015.
[6]郭明星.清开灵注射液解热作用代谢组学研究[D].北京:北京中医药大学,2014.
[7] Qin L,Zhang Z,Guo M,et al. Plasma metabolomics combined with lipidomics profiling reveals the potential antipyretic mechanisms of Qingkailing injection in a rat model[J].Chem Biol Interact,2016,254:24-33.
[8] Gao X,Guo M,Peng L,et al. UPLC Q-TOF-MS-Based Metabolic Profiling of Urine Reveals the Novel Antipyretic Mechanisms of Qingkailing Injection in a Rat Model of Yeast-Induced Pyrexia[J]. Evid Based Complement Alternat Med,2013:864747.
[9]周耀中,杨涛,季雪峰,等.基于UHPLC/MS的冠心病心绞痛血瘀证患者血清代谢组学研究[J].江西中医药,2018,6(50):25-28.
[10]周永峰,牛明,房吉祥,等.基于UPLC-Q-TOF-MS的五味子保肝作用代谢组学研究[J].中国中药杂志,2018,43(18):3756-3763.
[11]邵卫绪.基于代谢组学的抗心绞痛常见药物的比较[J].中国中医药现代远程教育,2014,12(10):100-102.
[12]郑磊.基于1H-NMR技术的黄连上清丸解热作用代谢组学研究[D].南昌:南昌大学,2014.
[13]杜丽娜.基于UPLC-MS技术的呼吸道合胞病毒肺炎痰热闭肺证代谢模式及金欣口服液干预研究[D].南京:南京中医药大学,2015.
[14]招树涛,甘智涛,黄丽霜.血清salusin-α及脂蛋白相关磷脂酶A2水平与颈动脉粥样硬化不稳定斑块患者并发脑梗死的相关性[J].临床和实验医学杂志,2018,17(11):1170-1172.
[15]王洪志,刘晓阳,于远军,等.缺血性脑血管病患者血清Lp-PLA2、Hcy及hs-CRP与颈动脉病变特点的相关性分析[J].疑难病杂志,2018,17(9):888-891,904.
[16]王晞.血清抗磷脂酶A2受体抗体在膜性肾病诊断中的应用价值[J].中国医药导报,2018,15(3):60-63.