[关键词]
[摘要]
目的 应用代谢组学技术结合病理学研究,探究肝、肺纤维化发生发展中共同生物标志物及其变化规律,阐释肝、肺纤维化“异病同治”的科学内涵。方法 以苏木精伊红(HE)染色检测肝、肺纤维化大鼠动态病理变化,并采用超高效液相色谱与四极杆-飞行时间串联质谱(UPLC-Q-TOF/MS)联用技术,分析其尿液代谢表达谱的动态变化,筛选分析影响肝、肺纤维化发生发展的共同潜在生物标志物及其变化规律,并阐释其生物学意义。结果 肝、肺纤维化存在相似的病理转归及代谢轨迹变化。其尿液中共有16种相同差异代谢物,其中肾上腺素红、5-L-谷酰基-牛磺酸等9种代谢物为关键生物标志物,主要通过参与氧化损伤、炎症、促纤维化因子释放共同影响肝、肺纤维化的发生发展。结论 代谢组学分析揭示了肝、肺纤维化共同生物标志物及其相同变化规律,从代谢物层面阐释其“异病同治”的科学内涵。
[Key word]
[Abstract]
Objective Urinary metabolomics associated with the histological progression of liver fibrosis (LF) and pulmonary fibrosis (PF) were utilized to explore common differential metabolites and their associated changes, and to explain the scientific connotation of the traditional Chinese medicine (TCM) theory of "homotherapy for heteropathy". Methods HE staining was used to monitor the histopathological changes in rats with LF and PF. Urinary metabolic profiling was performed by UPLC-Q-TOF/MS to analyze the metabolic profiles of LF and PF, as well as to clarify the common differential metabolites and their dynamic changes in LF and PF progression. Results Similar pathologic processes and trajectories of the PLS-DA score plots were observed in both the LF and PF models. Furthermore, 16 differential urine metabolites were found both in LF and PF. Among these, nine metabolites, including adrenochrome and 5-L-glutamyl-taurine, were key biomarkers which affect the development of LF and PF through oxidative damage, inflammation, and release of profibrogenic cytokines. Conclusion Metabonomic analysis revealed that LF and PF share common differential metabolites with the same changing trends and explained the scientific connotation of the TCM theory of "homotherapy for heteropathy".
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[基金项目]
国家重点基础研究发展(“973”)计划2013(CB531800);内蒙古自然科学基金项目(2017MS0813);包头医学院科学研究基金项目(BYJJ-QM 201652)