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脑心通通过 VEGF/eNOS 信号转导介导的血管新生抑制心肌梗死损伤。

Naoxintong inhibits myocardial infarction injury by VEGF/eNOS signaling-mediated neovascularization.

机构信息

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China; School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

出版信息

J Ethnopharmacol. 2017 Sep 14;209:13-23. doi: 10.1016/j.jep.2017.06.040. Epub 2017 Jun 30.

DOI:10.1016/j.jep.2017.06.040
PMID:28669772
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Naoxintong capsules (NXT), a traditional Chinese Medical preparation, are widely used for treatment of cardiovascular diseases, while the mechanism is still unclear.

MATERIALS AND METHODS

Myocardial infarction (MI) was induced by ligation of the left coronary artery in mice. Echocardiographic measurements were performed to do physiological assessments of left ventricle (LV) function. Histological and immunohistochemical staining was used to determine infarct size, capillary density, tissue endothelial nitric oxide synthase (eNOS) expression. Bone Marrow Transplantation (BMT) model and flow cytometric (FCM) analyses were applied to assay endothelial progenitor cells (EPCs) mobilization. Quantitative Real-Time Reverse Transcription Polymerase Chain Reaction (qRT-PCR), Western blotting and enzyme-linked immunosorbent assay (ELISA) were performed to detect the expressions of vascular endothelial growth factor (VEGF), kinase domain region (KDR), phosphorylated-Akt (p-Akt), phosphorylated-eNOS (p-eNOS).

RESULTS

NXT administration reduced myocardium fibrosis and increased myocardium capillary density in response to MI. NXT increased circulating Sca1/ Fetal liver kinase 1 (Flk1) mononuclear cells (MNCs) and soluble Kit ligand (sKitL) of bone marrow (BM) in response to MI. In mice transplanted with green fluorescent protein (GFP) BM cells, NXT increased the numbers of GFP-positive cells at the border zone of the ischemic region in MI-induced mice. NXT increased the numbers of eNOS-expressing BM-derived cells in tissues, which was involved in increased the expressions of VEGF, KDR, p-eNOS, p-Akt in the myocardium.

CONCLUSION

NXT-mediated recovery in MI-induced mice was involved in mobilization and incorporation of bone marrow-derived EPCs/circulating angiogenic cells (CACs) leading to enhancement of neovascularization via VEGF/eNOS signaling.

摘要

民族药理学相关性

脑心通胶囊(NXT)是一种传统的中药制剂,广泛用于治疗心血管疾病,但其作用机制尚不清楚。

材料和方法

通过结扎小鼠左冠状动脉诱导心肌梗死(MI)。进行超声心动图测量以对左心室(LV)功能进行生理评估。组织学和免疫组织化学染色用于确定梗死面积、毛细血管密度、组织内皮型一氧化氮合酶(eNOS)表达。骨髓移植(BMT)模型和流式细胞术(FCM)分析用于检测内皮祖细胞(EPC)动员。定量实时逆转录聚合酶链反应(qRT-PCR)、Western 印迹和酶联免疫吸附测定(ELISA)用于检测血管内皮生长因子(VEGF)、激酶结构域区域(KDR)、磷酸化-Akt(p-Akt)、磷酸化-eNOS(p-eNOS)的表达。

结果

NXT 给药可减少 MI 引起的心肌纤维化并增加心肌毛细血管密度。NXT 增加了 MI 时循环 Sca1/胎肝激酶 1(Flk1)单核细胞(MNC)和骨髓(BM)的可溶性 Kit 配体(sKitL)。在 GFP BM 细胞移植的小鼠中,NXT 增加了 GFP 阳性细胞在 MI 诱导的小鼠缺血区边界带的数量。NXT 增加了组织中表达 eNOS 的 BM 来源细胞的数量,这涉及增加了心肌中 VEGF、KDR、p-eNOS、p-Akt 的表达。

结论

NXT 介导的 MI 诱导小鼠的恢复涉及动员和整合骨髓来源的 EPCs/循环血管生成细胞(CACs),通过 VEGF/eNOS 信号增强新生血管形成。

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