Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Hunan Key Laboratory of Traditional Chinese Medicine for Gan of State Administration, Central South University, Changsha, Hunan, 410008, China.
Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
J Ethnopharmacol. 2019 Sep 15;241:111908. doi: 10.1016/j.jep.2019.111908. Epub 2019 Apr 25.
Blood-stasis syndrome (BSS) is a specific ZHENG type of coronary heart disease (CHD) in traditional Chinese medicine (TCM). The Xue-Fu-Zhu-Yu (XFZY) decoction is a common herbal formula that has been used for several centuries to treat BSS, but its mechanism has not been thoroughly elucidated to date.
In this study, serum lipid, blood haemorheology and metabolomics analyses were performed to depict a complete profile of XFZY capsules for the treatment of CHD with BSS and to reveal the potential mechanism of the XFZY capsules.
A rat model of CHD with BSS was generated by combining a high-fat diet (HFD) with a left anterior descending coronary artery (LAD) ligation. After four weeks of treatment with XFZY capsules or simvastatin pills, an echocardiography was performed for a therapeutic evaluation. Blood samples and heart tissues were then collected for further analyses. A UPLC-QTOF/MS-based metabolomics analysis of the plasma was performed, and all metabolic features were fit by PCA and OPLS-DA pattern for the biomarker screen. The identified biomarkers were later implemented into a metabolic pathway analysis. Furthermore, we used qRT-PCR and Western blot analyses to verify the treatment effects of the XFZY capsules.
A total of 49 metabolites (VIP>1.0, p < 0.05, RSD%<20%) were identified in the Model rats, and 27 metabolites (VIP>1.0, p < 0.05, RSD%<20%) were identified in the XFZY-H rats. The results of the pathway analysis indicated that the XFZY capsules treated CHD primarily by regulating cardiac energy, phospholipid, polyunsaturated fatty acid (PUFA) and amino acid metabolism. In addition, blood viscosity and serum lipid assays suggested that XFZY capsules could decrease serum triglycerides, total cholesterol, low-density lipoprotein cholesterol and whole blood viscosity at a low shear rate.
This study demonstrated that the XFZY capsule effectively decreases serum lipids and whole blood viscosity in CHD with BSS. The underlying metabolic mechanism mainly included improving cardiac energy supply, reducing phospholipid peroxide, maintaining the PUFA metabolic balance and regulating amino acid metabolism.
血瘀证（BSS）是中医（TCM）中冠心病（CHD）的一种特定证型。血府逐瘀（XFZY）汤是一种常用的草药配方，已使用数百年用于治疗 BSS，但迄今为止其机制尚未得到彻底阐明。
本研究通过血脂、血液流变学和代谢组学分析，描绘了 XFZY 胶囊治疗 BSS 型 CHD 的完整图谱，并揭示了 XFZY 胶囊的潜在机制。
采用高脂饮食（HFD）联合左前降支冠状动脉（LAD）结扎法建立 CHD 伴 BSS 大鼠模型。经 XFZY 胶囊或辛伐他汀片治疗 4 周后，进行超声心动图治疗评价。然后收集血液样本和心脏组织进行进一步分析。采用 UPLC-QTOF/MS 代谢组学分析血浆，采用 PCA 和 OPLS-DA 模式对所有代谢特征进行拟合，以筛选生物标志物。随后将鉴定出的生物标志物进行代谢途径分析。此外，我们还采用 qRT-PCR 和 Western blot 分析验证 XFZY 胶囊的治疗效果。
模型大鼠中鉴定出 49 种代谢物（VIP>1.0，p<0.05，RSD%<20%），XFZY-H 大鼠中鉴定出 27 种代谢物（VIP>1.0，p<0.05，RSD%<20%）。途径分析结果表明，XFZY 胶囊主要通过调节心脏能量、磷脂、多不饱和脂肪酸（PUFA）和氨基酸代谢来治疗 CHD。此外，血液黏度和血脂检测结果表明，XFZY 胶囊可降低 CHD 伴 BSS 大鼠的血清甘油三酯、总胆固醇、低密度脂蛋白胆固醇和低切全血黏度。
本研究表明，XFZY 胶囊可有效降低 CHD 伴 BSS 大鼠的血脂和全血黏度。其潜在的代谢机制主要包括改善心脏能量供应、减少磷脂过氧化、维持 PUFA 代谢平衡和调节氨基酸代谢。
