基于中医代谢组学特征探讨参苓白术丸联合黄芪颗粒干预肺纤维化的作用机制

Exploration of Therapeutic Mechanism of Shenling Baizhu Pills Combined with Huangqi Granules on Intervening Pulmonary Fibrosis Based on Characteristics of Traditional Chinese Medicine Metabolomics

【目的】基于中医代谢组学特征探讨参苓白术丸联合黄芪颗粒干预肺纤维化的作用机制。【方法】选取23例肺纤维化肺脾气虚证患者为肺纤维化组,另选取20例健康体检者为对照组。肺纤维化组给予参苓白术丸联合黄芪颗粒治疗2个月,对照组不给予任何干预治疗。观察肺纤维化组患者治疗前后中医证候评分的变化情况,分析肺纤维化组与对照组的血浆代谢差异物成分。【结果】(1)治疗2个月后,肺纤维化组患者喘息、咳嗽、自汗、乏力评分均较治疗前明显改善,差异均有统计学意义(P<0.01)。(2)推测出在正离子模式下,磷脂酰胆碱、溶血磷脂酸、基质金属蛋白酶1、白三烯4、脂氧素15-epiLXB4、15-羟基二十碳四烯酸6种物质为肺纤维化组干预后的差异性代谢物,神经酰胺酶、磷脂酶为其主要代谢通路。【结论】参苓白术丸联合黄芪颗粒治疗肺纤维化后对脂类代谢物质(磷脂酰胆碱、溶血磷脂酸、脂氧素15-epi-LXB4)改善显著,表明脂类代谢异常与肺纤维化的发生发展有密切联系。参苓白术丸联合黄芪颗粒能显著改善肺纤维化患者临床症状,通过神经酰胺酶、磷脂酶通路参与肺纤维化发病过程,表明神经酰胺酶、磷脂酶类代谢通路的差异性是肺纤维化炎症等症状存在的基础,进一步证实了以神经酰胺酶、磷脂酶为代表的鞘磷脂类代谢通路的差异性是参与肺纤维化疾病发展过程中的主要通路所在。

Objective To explore the mechanism of Shenling Baizhu Pills combined with Huangqi Granules on intervening the pulmonary fibrosis based on the characteristics of traditional Chinese medicine(TCM)metabolomics. Methods Twenty-three cases of pulmonary fibrosis patients with lung-spleen qi deficiency syndrome served as the case group, and 20 healthy volunteers showed by physical examination served as the healthy control group. The case group was treated with Shenling Baizhu Pills combined with Huangqi Granules for 2 months,while the healthy control group was not given any intervention. The changes in the traditional Chinese medicine(TCM)syndrome scores of the two groups before and after treatment were observed, and the plasma differential metabolites in the two groups were analyzed. Results(1)After treatment for 2 months,the scores of dyspnea,cough,spontaneous sweating,and weakness in the case group were much improved as compared with those before treatment, and the differences were statistically significant(P<0.01).(2)It was speculated that under the positive ion mode, the six substances of phosphatidylcholine, lysophosphatidic acid, matrix metalloproteinase-1, leukotriene-4, lipoxygenin 15-epi-LXB4, and 15-hydroxycosahexaenoic acid were present as the components of plasma differential metabolites in the case group after intervention,and the main metabolic pathways involved ceramidase and phospholipase. Conclusion Shenling Baizhu Pills combined with Huangqi Granules can significantly improve lipid metabolites of phosphatidylcholine,lysophosphatidic acid,and lipoxygenin 15-epi-LXB4 in the treatment of pulmonary fibrosis,which indicates that abnormal lipid metabolism is closely related to the occurrence and development of pulmonary fibrosis. Shenling Baizhu Pills combined with Huangqi Granules can significantly relieve the clinical symptoms of patients with pulmonary fibrosis, and participate in the pathogenesis of pulmonary fibrosis through ceramidase and phospholipase pathways,indicating that the difference of ceramidase and phospholipase metabolic pathways is the pathogenesis basis of the occurrence of symptoms such as pulmonary fibrosis inflammation,and further confirming that the differential sphingolipids metabolic pathway represented by ceramidase and phospholipase is the main pathway involved in the development of pulmonary fibrosis.