中文摘要：传统的中药配方定心方（DXR）可安全有效地治疗心血管疾病，如心律失常、冠心病。按传统用法对定心方进行改进，得到定心方IV，但后者对动脉粥样硬化的反应机理尚不明确。本研究旨在阐明DXR IV是否能通过调节脂类代谢及肠道微生物以改善动脉粥样硬化小鼠的症状。研究发现，DXR IV具有潜在的抗动脉粥样硬化作用，此作用与脂质代谢和肠道微生物群密切相关，为DXR-IV治疗动脉粥样硬化的机制提供了新的认识，并为临床应用提供了依据。
外文摘要：Ethnopharmacological relevance: Dingxin Recipe (DXR) is a traditional Chinese medicine formula that has been reported to be effective and safe treatment for cardiovascular diseases, such as arrhythmias, coronary heart disease. Dingxin Recipe IV (DXR IV) was further improved from the DXR according to the traditional use. However, the mechanism of DXR IV in atherosclerosis is unclear.
   Aim of the study: This study aimed to illustrate whether DXR IV improve atherosclerosis through modulating the lipid metabolism and gut microbiota in atherosclerosis mice.
   Materials and methods: 40 male ApoE-/mice were fed on HFD for 12 weeks and were then treated with DXR IV (1.8, 0.9, or 0.45 g/kg/d) for another 12 weeks. The decroation of DXR IV contains four traditional Chinese medicines: the dried rhizome of Coptis chinensis Franch. (15.09%), the root of Salvia miltiorrhiza Bunge (28.30%), the seed of Ziziphus jujuba Mill. (37.74%) and the fruiting body of Ganoderma lucidum (Leyss.ex Fr.) Karst. (18.87%). 8 male c57BL/6 mice fed a normal diet served as control group. The atherosclerotic plaque was quantified by oil-red O staining and masson trichrome staining. Mice feces were collected. The gut micobiota were detected by 16S rRNA gene sequencing and fecal metabolites were analyzed by 1H NMR spectroscopy. The effect of DXR IV on blood lipids (TG, TC, LDL-C, HDL-C) was investigated. The lipid metabolism related genes were determined by RT-qPCR and western blotting respectively.
   Results: DXR IV exerted the anti-atherosclerosis effect by inhibiting the excessive cholesterol deposition in aorta and regulating the level of TG, TC, LDL-C and HDL-C. The composition of gut microbiota was changed. Interestingly, the relative abundance of Muribaculaceae and Ruminococcaceae increased after DXR IV administration, whereas the abundance of Erysipelotrichaceae decreased, which have been beneficial to lipid metabolism. Nine potential metabolic biomarkers, including acetate, butyrate, propionate, alanine, succinate, valerate, xylose, choline, glutamate, were identified, which were related to fatty acid metabolism. Further, the pathway of fatty acid was detected by the RT-qPCR and western blotting. Compared with model group, the level of LXR-alpha and SREBP1 decreased significantly in DXR IV group while LXR-beta, SREBP2 showed no statistical significance. It indicated that DXR IV modulated lipid metabolism by LXR-alpha/SREBP1 but not LXR beta and SREBP2.
   Conclusions: DXR IV exhibits potential anti-atherosclerosis effect, which is closely related to lipid metabolism and the gut microbiota. This study may provide novel insights into the mechanism of DXR IV on atherosclerosis and a basis for promising clinical usage.
外文关键词：Atherosclerosis; Gut microbiota; Dingxin recipe IV; Lipid metabolism; Traditional Chinese medicine
作者：Zhang, YX；Gu, YY；Chen, YH；Huang, ZY；Li, M；Jiang, WH；Chen, JH；Rao, WT；Luo, SF；Chen, YY；Chen, JQ；Li, LJ；Jia, YH；Liu, MH；Zhou, FH
作者单位：Southern Med Univ；Sun Yat Sen Univ；982 Hosp PLA
期刊名称：JOURNAL OF ETHNOPHARMACOLOGY
期刊影响因子：3.69
出版年份：2021
出版刊次：266
点击下载：定心方IV通过LXR-α/SREBP1信号通道调节饲喂HFD的ApoE（-/-）小鼠脂类代谢及肠道微生物，从而改善动脉粥样硬化症