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补阳还五汤通过靶向血管生成通路对急性心肌梗死小鼠的心脏保护作用。

Buyang Huanwu Decoction Exerts Cardioprotective Effects through Targeting Angiogenesis via Caveolin-1/VEGF Signaling Pathway in Mice with Acute Myocardial Infarction.

机构信息

Department of Cardiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.

出版信息

Oxid Med Cell Longev. 2019 Apr 16;2019:4275984. doi: 10.1155/2019/4275984. eCollection 2019.

DOI:10.1155/2019/4275984
PMID:31178960
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6501136/
Abstract

BACKGROUND

Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. The idea of therapeutic angiogenesis in ischemic myocardium is a promising strategy for MI patients. Buyang Huanwu decoction (BHD), a famous Chinese herbal prescription, exerted antioxidant, antiapoptotic, and anti-inflammatory effects, which contribute to cardio-/cerebral protection. Here, we aim to investigate the effects of BHD on angiogenesis through the caveolin-1 (Cav-1)/vascular endothelial growth factor (VEGF) pathway in MI model of mice.

MATERIALS AND METHODS

C57BL/6 mice were randomly divided into 3 groups by the table of random number: (1) sham-operated group (sham, = 15), (2) AMI group (AMI+sham, = 20), and (3) BHD-treated group (AMI+BHD, = 20). 2,3,5-Triphenyltetrazolium chloride solution stain was used to determine myocardial infarct size. Myocardial histopathology was tested using Masson staining and hematoxylin-eosin staining. CD31 immunofluorescence staining was used to analyze the angiogenesis in the infarction border zone. Western blot analysis, immunofluorescence staining, and/or real-time quantitative reverse transcription polymerase chain reaction was applied to test the expression of Cav-1, VEGF, vascular endothelial growth factor receptor 2 (VEGFR2), and/or phosphorylated extracellular signal-regulated kinase (p-ERK). All statistical analyses were performed using the SPSS 20.0 software and GraphPad Prism 6.05. Values of < 0.05 were considered as statistically significant.

RESULTS AND CONCLUSION

Compared with the AMI group, the BHD-treated group showed a significant improvement in the heart weight/body weight ratio, echocardiography images, cardiac function, infarct size, Mason staining of the collagen deposition area, and density of microvessel in the infarction border zone ( < 0.05). Compared with the AMI group, BHD promoted the expression of Cav-1, VEGF, VEGFR2, and p-ERK in the infarction border zone after AMI. BHD could exert cardioprotective effects on the mouse model with AMI through targeting angiogenesis via Cav-1/VEGF signaling pathway.

摘要

背景

急性心肌梗死(AMI)仍然是全球发病率和死亡率的主要原因。在缺血心肌中进行治疗性血管生成的想法是 MI 患者的一种有前途的策略。补阳还五汤(BHD)是一种著名的中药方剂,具有抗氧化、抗凋亡和抗炎作用,有助于心脏/大脑保护。在这里,我们旨在通过 Cav-1/血管内皮生长因子(VEGF)通路研究 BHD 对 MI 模型中小鼠血管生成的影响。

材料和方法

C57BL/6 小鼠通过随机数表随机分为 3 组:(1)假手术组(sham,n=15)、(2)AMI 组(AMI+sham,n=20)和(3)BHD 治疗组(AMI+BHD,n=20)。2,3,5-三苯基氯化四氮唑溶液染色用于确定心肌梗死面积。采用 Masson 染色和苏木精-伊红染色检测心肌组织病理学变化。CD31 免疫荧光染色用于分析梗死边界区的血管生成。Western blot 分析、免疫荧光染色和/或实时定量逆转录聚合酶链反应用于检测 Cav-1、VEGF、血管内皮生长因子受体 2(VEGFR2)和/或磷酸化细胞外信号调节激酶(p-ERK)的表达。所有统计分析均使用 SPSS 20.0 软件和 GraphPad Prism 6.05 进行。 < 0.05 被认为具有统计学意义。

结果和结论

与 AMI 组相比,BHD 治疗组的心脏重量/体重比、超声心动图图像、心功能、梗死面积、胶原沉积区 Mason 染色和梗死边界区微血管密度均有显著改善( < 0.05)。与 AMI 组相比,BHD 促进了 AMI 后梗死边界区 Cav-1、VEGF、VEGFR2 和 p-ERK 的表达。BHD 可能通过靶向 Cav-1/VEGF 信号通路促进血管生成,对 AMI 小鼠模型发挥心脏保护作用。

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