毛蕊异黄酮对大鼠心肌缺血再灌注损伤的保护作用机制研究

Study of protective mechanism of calycosinon on myocardial ischemia-reperfusion injury in rats

关键词:  毛蕊异黄酮  缺血再灌注  Nrf2/HO-1通路

Key words:  calycosin  ischemia-reperfusion  Nrf2/HO-1 signaling pathway

摘要:

[目的]明确毛蕊异黄酮对大鼠心肌缺血再灌注损伤的保护作用机制。[方法]使用Langendorff装置制备心肌缺血再灌注损伤模型，实时监测心功能参数，并检测冠脉流出液中冠脉流量（CK）、心功能参数（LDH）以及心脏组织中MDA和SOD水平；TTC染色方法观察组织病理学损伤；采用Western Blot考察毛蕊异黄酮对氧化应激状态下的Nrf2、HO-1、AKT、ERK蛋白表达影响。[结果]毛蕊异黄酮能显著增加缺血再灌注损伤模型大鼠心脏冠脉流量、左室发展压和最大上升/下降速率的变化率，从而改善大鼠心功能。同时降低冠脉流出液中CK、LDH水平和心肌组织中两二醛（MDA）含量，增加超氧化物歧化酶（SOD）、琥珀酸脱氢酶（SDH）等抗氧化酶的活力；并通过激活Nrf2基因，从而调节其下游的抗氧化基因。[结论]毛蕊异黄酮通过激活Nrf2/HO-1信号通路发挥抗氧化应激作用，进而改善大鼠心肌缺血再灌注损伤，发挥保护心肌作用。

Abstract:

[Objective] To study the protective mechanism of calycosinon myocardial ischemia-reperfusion injury in rats.[Methods] Myocardial ischemia reperfusion injury model established using the Langendorff device. The parameters of cardiac function were monitored in real-time; the level of LDH and CK in coronary effluent fluid, MDA and SOD in heart tissue were detected. The pathological damage of myocardial tissue was observed by staining with TTC. At the same time, the effects of calycosin on the protein expression of Nrf2, HO-1 were investigated by Western blot.[Results] Calycosincan significantly increase coronary flowrate, left ventricular development pressure, maximal ascending/descending rate, and improved cardiac function in the model of ischemia-reperfusion injury, decreased the levels of CK and LDH in coronary effluent, while increased antioxidant enzymes activity such as MDA, SOD and SDH including downstream regulation of the antioxidant genes by activating the Nrf2 gene.[Conclusion] Calycosin played a role in anti-oxidativestress by activating the Nrf2/HO-1 signaling pathway, and then protected myocardial from ischemic-reperfused injury.