Acupuncture and Tuina college, Nanjing University of Chinese Medicine, Nanjing, China.
Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China.
PLoS One. 2020 May 4;15(5):e0231797. doi: 10.1371/journal.pone.0231797. eCollection 2020.
The pathological process and mechanism of myocardial ischemia (MI) is very complicated, and remains unclear. An integrated proteomic-metabolomics analysis was applied to comprehensively understand the pathological changes and mechanism of MI. Male Sprague-Dawley rats were randomly divided into a mock surgery (MS) group and an MI group. The MI model was made by ligating the left anterior descending coronary artery, twenty-four hours after which, echocardiography was employed to assess left ventricular (LV) function variables. Blood samples and left ventricular tissues were collected for ELISA, metabolomics and proteomics analysis. The results showed that LV function, including ejection fraction (EF) and fractional shortening (FS), was significantly reduced and the level of cTnT in the serum increased after MI. iTRAQ proteomics showed that a total of 169 proteins were altered including 52 and 117 proteins with increased and decreased expression, respectively, which were mainly involved in the following activities: complement and coagulation cascades, tight junction, regulation of actin cytoskeleton, MAPK signaling pathway, endocytosis, NOD-like receptor signaling pathway, as well as phagosome coupled with vitamin digestion and absorption. Altered metabolomic profiling of this transition was mostly enriched in pathways including ABC transporters, glycerophospholipid metabolism, protein digestion and absorption and aminoacyl-tRNA biosynthesis. The integrated metabolomics and proteomics analysis indicated that myocardial injury after MI is closely related to several metabolic pathways, especially energy metabolism, amino acid metabolism, vascular smooth muscle contraction, gap junction and neuroactive ligand-receptor interaction. These findings may contribute to understanding the mechanism of MI and have implication for new therapeutic targets.
心肌缺血（MI）的病理过程和机制非常复杂，目前尚不清楚。本研究采用整合的蛋白质组学-代谢组学分析方法，全面了解 MI 的病理变化和机制。雄性 Sprague-Dawley 大鼠随机分为假手术（MS）组和 MI 组。结扎左前降支冠状动脉制作 MI 模型，24 小时后，采用超声心动图评估左心室（LV）功能变量。采集血样和左心室组织，进行 ELISA、代谢组学和蛋白质组学分析。结果显示，MI 后 LV 功能（包括射血分数 EF 和缩短分数 FS）显著降低，血清 cTnT 水平升高。iTRAQ 蛋白质组学显示，共有 169 种蛋白质发生改变，其中 52 种和 117 种蛋白质表达上调和下调，主要涉及以下活动：补体和凝血级联反应、紧密连接、肌动蛋白细胞骨架调节、MAPK 信号通路、内吞作用、NOD 样受体信号通路以及吞噬体与维生素消化吸收的偶联。这种转变的代谢组学特征主要富集在 ABC 转运蛋白、甘油磷脂代谢、蛋白质消化吸收和氨酰-tRNA 生物合成等途径中。整合的代谢组学和蛋白质组学分析表明，MI 后心肌损伤与几种代谢途径密切相关，特别是能量代谢、氨基酸代谢、血管平滑肌收缩、间隙连接和神经活性配体-受体相互作用。这些发现可能有助于理解 MI 的机制，并为新的治疗靶点提供启示。
