Sun Hui, Li Xue-Na, Zhang Ai-Hua, Zhang Kun-Ming, Yan Guang-Li, Han Ying, Wu Fang-Fang, Wang Xi-Jun
National Chinmedomics Research Center, Sino-America Chinmedomics Technology Collaboration Center, National TCM Key Laboratory of Serum Pharmacochemistry, Laboratory of Metabolomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine Heping Road 24 Harbin China
National Engineering Laboratory for the Development of Southwestern Endangered Medicinal Materials, Guangxi Botanical Garden of Medicinal Plant Nanning Guangxi China.
RSC Adv. 2019 Apr 11;9(20):11420-11432. doi: 10.1039/c8ra10557j. eCollection 2019 Apr 9.
Coronary heart disease (CHD) is a relatively complex disease characterized by narrowing of the arterial lumen and reduction of blood flow to the heart. There is no effective early diagnosis and prevention method. Jing Zhi Guan Xin Pian (JZGXP) is a new preparation prepared from the effective extract of Guanxin II. It is made of five components of traditional Chinese medicine and functions by promoting blood circulation and removing blood stasis and is used for the treatment of CHD and angina pectoris. In our study, a CHD rat model was prepared using a high-fat diet combined with intraperitoneal injection of vitamin D3. Clinical biochemical indexes (TG, CHO and HDL-C), histopathology (coronary and myocardial tissue), electrocardiogram and cardiac indexes were used to evaluate the efficacy of JZGXP in the treatment of CHD model rats. UPLC-HDMS-based metabolomics techniques were used to find metabolic profiles, biomarkers and related metabolic pathways in CHD models and to evaluate the effects of JZGXP on them. At the same time, the targets of JZGXP for the treatment of CHD were analyzed. Our study ultimately identified 25 biomarkers associated with CHD models. Further studies found that these 25 biomarkers involved 9 metabolic pathways in the body and found that JZGXP can recall 21 biomarkers in the urine of model rats and these biomarkers involve nine metabolic pathways. Finally, the targets of JZGXP for the treatment of CHD were β-alanine metabolism and tyrosine metabolism, amino acids metabolism. This study showed that metabolomics technology is effective for exploring potential biomarkers associated with syndromes or diseases and the therapeutic mechanisms of a traditional Chinese medicine formulation.
冠心病（CHD）是一种相对复杂的疾病，其特征是动脉管腔狭窄和心脏血流量减少。目前尚无有效的早期诊断和预防方法。精制冠心片（JZGXP）是由冠心II号有效提取物制备的新制剂。它由五种中药成分组成，具有活血化瘀的功效，用于治疗冠心病和心绞痛。在我们的研究中，采用高脂饮食联合腹腔注射维生素D3制备冠心病大鼠模型。通过临床生化指标（TG、CHO和HDL-C）、组织病理学（冠状动脉和心肌组织）、心电图和心脏指标来评估JZGXP对冠心病模型大鼠的治疗效果。基于超高效液相色谱-高分辨质谱的代谢组学技术用于寻找冠心病模型中的代谢谱、生物标志物和相关代谢途径，并评估JZGXP对它们的影响。同时，分析JZGXP治疗冠心病的靶点。我们的研究最终确定了25个与冠心病模型相关的生物标志物。进一步研究发现，这25个生物标志物涉及体内9条代谢途径，且发现JZGXP能使模型大鼠尿液中的21个生物标志物恢复正常，这些生物标志物涉及9条代谢途径。最后，JZGXP治疗冠心病的靶点为β-丙氨酸代谢、酪氨酸代谢和氨基酸代谢。本研究表明，代谢组学技术对于探索与证候或疾病相关的潜在生物标志物以及中药制剂的治疗机制是有效的。
