病理与生理状态下化痰降气胶囊大鼠血清移行成分对比研究

采用UPLC-Q-TOF-MS技术,分析化痰降气胶囊在生理和慢性阻塞性肺疾病(COPD)状态下大鼠的移行成分及其体内代谢过程的差异。通过烟熏复合气管滴入脂多糖法建立COPD大鼠模型,分别给予正常和模型大鼠化痰降气胶囊,灌胃给药,肝门静脉采血,经样品处理后,制得含药血清样品。将制得的10批化痰降气胶囊含药血清样品,进行UPLC分析,评价含药血清的质量稳定性。运用UPLC-Q-TOF-MS,进行移行成分质谱信息采集。该研究鉴定了正常大鼠化痰降气胶囊血清移行成分28个,COPD模型大鼠化痰降气胶囊血清移行成分25个,两者既存在相同移行成分,也存在差异移行成分;进一步研究发现2种状态下大鼠的移行成分的体内代谢过程也存在差异,在正常大鼠中,移行成分的代谢类型多以Ⅰ相反应居多,在COPD模型大鼠中,Ⅰ相反应相应减少,Ⅱ相反应相应增加。该研究借助UPLC-Q-TOF-MS技术,分析了在生理和病理状态下化痰降气胶囊的大鼠血清移行成分及其体内代谢过程的差异,表明在COPD病理状态下,血清移行成分会出现差异,体内一些代谢酶的活性会发生改变,进而影响药物在体内的代谢转化过程,为进一步阐明化痰降气胶囊的体内代谢过程及药效物质基础奠定了基础。

Comparative study on serum transitional components of Huatan Jiangqi Capsules in rats under pathological and physiological status

The differences of transitional components and metabolic processes of Huatan Jiangqi Capsules(HTJQ)in rats under normal physiological and pathological conditions of COPD were analyzed by UPLC-Q-TOF-MS.The rat COPD model was established by passive smoking and intratracheal instillation of lipopolysaccharide.After the normal and COPD model rats were douched with HTJQ,the blood was collected from hepatic portal vein and the drug-containing serum samples were prepared by methanol precipitation of protein.Then,10 batches of drug-containing serum samples of HTJQ were prepared and analyzed by UPLC serum fingerprint to evaluate the quality and stability of drug-containing serum samples.UPLC-Q-TOF-MS was used to collect the mass spectrometric information of the transitional components.Twenty-eight transitional components of HTJQ in normal rats and 25 transitional components of HTJQ in COPD model rats were identified by UPLC-Q-TOF-MS.Under pathological and physiological conditions,there were not only the same transitional components in rat serum,but also corresponding differences.Further studies showed that there were also differences in the metabolic process of transitional components between the two conditions.In normal rats,most of the metabolic types of transitional components were phase I reactions.In COPD model rats,phaseⅠreactions decreased and phaseⅡreactions increased correspondingly.With UPLC-Q-TOF-MS technology,the differences of transitional components and the metabolism process of HTJQ in rats under normal physiological and pathological conditions were analyzed.The results showed that types of transitional components and the activity of some metabolic enzymes would be changed in COPD pathological state,which would affect the metabolic process of bioactive components in vivo.It laid a foundation for further elucidating the metabolic process and pharmacodynamic substance basis of HTJQ.