Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China 100700.
Zunyi Medical University, Zunyi, China 563000.
Oxid Med Cell Longev. 2022 Jul 23;2022:3712500. doi: 10.1155/2022/3712500. eCollection 2022.
In myocardial ischemia, optimizing the myocardial metabolic phenotype to improve cardiac function is critical. Naoxintong capsules (NXT) are widely prescribed in Chinese medicine for the treatment of cerebrovascular and cardiovascular diseases.
In this study, a rat model of myocardial infarction was established by ligation of the left anterior descending coronary artery. The structure and function of the heart were evaluated using echocardiography. The pathological changes of the rat myocardium and the myocardial volume collagen fraction (CVF) were examined using hematoxylin-eosin (HE) and Masson's trichrome staining (Masson). The expression of TNF- and IL-6 were detected by immunohistochemistry. The level of cTnT was also measured to evaluate myocardial injury. In order to study the changes in energy metabolism in myocardial infarction and the effects of NXT, a targeted analysis method for detecting the 29 energy metabolites in cardiac muscle tissue was developed based on UPLC-QQQ-MS. Western blotting was used to detect the expression of proteins related to energy metabolism in myocardia.
In the rat model of myocardial infarction, NXT showed obvious effects, such as improving heart function and increasing LVEF and LVFS. HE staining, Masson staining, and immunohistochemical results revealed that NXT decreased inflammatory infiltration, improved myocardial fibrosis, and reduced infarct size. In addition, NXT significantly reduced the level of serum cTnT. The levels of the 29 energy metabolites in cardiac muscle tissue were analyzed using a newly developed targeted analysis method. Compared to the sham group, the levels of 17 metabolites from different energy metabolic pathways, including four compounds in glycolysis metabolism, four compounds in TCA cycle, three compounds in oxidative phosphorylation, four compounds in purine metabolism, and two compounds in glutathione metabolism, displayed obvious changes induced by myocardial ischemia. Expressions of SIRT1, PGC-1, and ATP5D proteins related to energy metabolism were decreased after myocardial infarction. These perturbations could all be reversed by NXT intervention, suggesting that the therapeutic effects of NXT were partially due to interferences with energy metabolisms.
This study provides a useful approach for investigating the mechanism of myocardial infarction and evaluating the efficacy of NXT from energy metabolism.
在心肌缺血中，优化心肌代谢表型以改善心功能至关重要。脑心通胶囊（NXT）在中药中广泛用于治疗心脑血管疾病。
本研究通过结扎左前降支冠状动脉建立大鼠心肌梗死模型，利用超声心动图评估心脏的结构和功能。通过苏木精-伊红（HE）和 Masson 三色染色（Masson）观察大鼠心肌的病理变化和心肌容积胶原分数（CVF）。免疫组织化学法检测 TNF-α和 IL-6 的表达。测定 cTnT 水平评估心肌损伤。为了研究心肌梗死中心肌能量代谢的变化及 NXT 的作用，建立了基于 UPLC-QQQ-MS 的心肌组织中 29 种能量代谢物的靶向分析方法。Western blot 法检测心肌能量代谢相关蛋白的表达。
在大鼠心肌梗死模型中，NXT 表现出明显的效果，如改善心功能、增加 LVEF 和 LVFS。HE 染色、Masson 染色和免疫组化结果显示，NXT 减少了炎症浸润，改善了心肌纤维化，减少了梗死面积。此外，NXT 显著降低了血清 cTnT 水平。采用新建立的靶向分析方法对心肌组织中 29 种能量代谢物进行分析。与假手术组相比，17 种不同能量代谢途径的代谢物水平发生明显变化，包括糖酵解代谢中的 4 种化合物、三羧酸循环中的 4 种化合物、氧化磷酸化中的 3 种化合物、嘌呤代谢中的 4 种化合物和谷胱甘肽代谢中的 2 种化合物。心肌缺血诱导的代谢物水平发生明显变化。心肌梗死后，SIRT1、PGC-1 和 ATP5D 等与能量代谢相关的蛋白表达降低。这些变化均可通过 NXT 干预得到逆转，提示 NXT 的治疗作用部分是通过干扰能量代谢实现的。
本研究为从能量代谢角度研究心肌梗死的机制和评价 NXT 的疗效提供了一种有用的方法。
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