丹酚酸 B 和人参皂苷 Rg1 联合对亚急性心肌梗死的心脏保护作用及其机制。
Cardioprotection of salvianolic acid B and ginsenoside Rg1 combination on subacute myocardial infarction and the underlying mechanism.
机构信息
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
出版信息
Phytomedicine. 2019 Apr;57:255-261. doi: 10.1016/j.phymed.2018.12.040. Epub 2018 Dec 31.
BACKGROUND
Following myocardial infarction (MI), a series of structural and functional changes evolves in the myocardium, collectively defined as cardiac remodeling.
PURPOSE
The aim of present study was to investigate the cardioprotection of salvianolicacid B (SalB) and ginsenoside Rg1 (Rg1) combination against cardiac remodeling in a rat model at the subacute phase of MI and further elucidate the underlying mechanism.
METHODS
Rat heart was exposed via a left thoracotomy at the fourth intercostal space and MI was induced by a ligature below the left descending coronary artery. Hemodynamic assay was conducted using a Mikro-tipped SPR-320 catheter which was inserted through the right carotid artery into left ventricle.Myocardial infarct size was detected using 3,5-triphenyltetrazolium chloride (TTC) staining. Haematoxylin and eosin (HE) stain and picric sirius red stain were conducted for histopathological detection. Immunohistochemistry was used to detect the expression of α-smooth muscle actin (α-SMA) and gelatin zymography was used to evaluate the activities of matrix metalloproteinase-9 (MMP-9).
RESULTS
Comparing with MI rats, 30 mg/kg SalB-Rg1 improved cardiac function verified by maximum rate of pressure development for contraction (+dp/dt, p < 0.01) and maximum rate of pressure development for relaxation (-dp/dt, p < 0.05); reduced myocardial infarct size (p < 0.05) verified by TTC staining, improved cardiac structure based on HE stain; decreased collagen volume fraction (p < 0.05) and collagen I/III ratio (p < 0.05) according picrosirius red staining. The underlying mechanism of SalB-Rg1 against cardiac remodeling was associated with its down-regulation on α-SMA expression according immunohistochemistry (p < 0.01) and inhibition on MMP-9 activity based on in-gel zymography (p < 0.05).
CONCLUSION
All above study indicated the potential therapeutic effects of SalB-Rg1 on heart.
背景
心肌梗死后，心肌会发生一系列结构和功能改变，统称为心脏重构。
目的
本研究旨在探讨丹参素 B（SalB）和人参皂苷 Rg1（Rg1）联合用药对心肌梗死后亚急性期大鼠心脏重构的保护作用，并进一步阐明其作用机制。
方法
通过第四肋间开胸暴露大鼠心脏，结扎左冠状动脉前降支下方的冠状动脉，诱导心肌梗死。通过将 Mikro-tipped SPR-320 导管从右侧颈动脉插入左心室，进行血流动力学检测。采用 3,5-三苯基四氮唑氯化物（TTC）染色检测心肌梗死面积。进行苏木精和伊红（HE）染色和苦味酸天狼猩红染色进行组织病理学检测。采用免疫组化法检测α-平滑肌肌动蛋白（α-SMA）的表达，明胶酶谱法检测基质金属蛋白酶-9（MMP-9）的活性。
结果
与心肌梗死大鼠相比，30mg/kg SalB-Rg1 改善了心脏功能，表现为收缩期最大压力发展速率（+dp/dt，p<0.01）和舒张期最大压力发展速率（-dp/dt，p<0.05）的提高；TTC 染色证实心肌梗死面积减小（p<0.05），HE 染色证实心脏结构改善；苦味酸天狼猩红染色显示胶原容积分数（p<0.05）和胶原 I/III 比值（p<0.05）降低。SalB-Rg1 防治心脏重构的机制与其免疫组化染色中α-SMA 表达下调（p<0.01）和明胶酶谱中 MMP-9 活性抑制（p<0.05）有关。
结论
本研究表明 SalB-Rg1 对心脏具有潜在的治疗作用。
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