N-乙酰半胱氨酸在大鼠心肌缺血损伤中保护作用的研究

N-acetylcysteine attenuates isoproterenol induced rat heart ischemia injury

目的:探讨N-乙酰半胱氨酸(N-acetylcysteine,NAC)对大鼠心肌缺血损伤的保护作用。方法:采用150 mg.kg-1.d-1异丙肾上腺素皮下注射建立Wistar大鼠心肌缺血损伤的模型,以心脏超声、DHE染色、Western blot、实时定量RT-PCR、免疫组化等实验方法,检测NAC对心功能,氧自由基、细胞凋亡、超氧化物歧化酶-1(SOD-1)表达、血小板衍生生长因子受体β(PDGFRβ)表达的影响。结果:大鼠皮下注射异丙肾上腺素后出现心肌缺血损伤,血清LDH增高,心肌组织氧自由基生成明显升高,心肌细胞凋亡明显增加,SOD-1减少,PDGFRβ表达增加,与正常组相比差异具有统计学意义(P<0.05);与异丙肾上腺素处理组比较,NAC(200 mg.kg-1.d-1)预处理后心肌损伤减轻,氧自由基生成降低,凋亡细胞减少,PDGFRβ表达降低,SOD-1表达水平明显增高。结论:抗氧化剂NAC可以通过抑制心肌氧化应激,减少氧自由基生成和心肌细胞凋亡,对异丙肾上腺素诱导的大鼠心肌缺血损伤发挥保护作用。

Objective：To investigate the protective effect of N-acetylcysteine（NAC） on isoproterenol induced rat myocardial ischemia.Methods： The myocardial ischemia model was developed by（150 mg·kg-1·d-1） of isoproterenol subcutaneous injection for 3d in Wistar rat.The heart function,reactive oxygen species（ROS） production,cell apoptotosis,superoxide dismutase（SOD-1） and platelet-derived growth factor receptorβ（PDGFRβ） expression were analyzed by Echo,DHE staining,real-time RT-PCR,Western blot and immunohistochemistry staining.Results： The serum LDH,myocardial ROS production,cell apoptosis rate and PDGFRβ expression were increased obviously after isoproterenol injection,whereas the heart function and SOD-1 expression were decreased significantly.In rat pretreated with（200 mg·kg-1·d-1 N-acetylcysteine and then injected with isoproterenol,serum LDH,ROS production,cell apoptosis and PDGFRβ expression were decreased;and heart function and SOD-1 expression were increased.Conclusion： The results suggest that N-acetylcysteine could attenuate oxidative stress,cell apoptosis,PDGFRβ expression and increase SOD-1 expression to protect the rat heart from isoproterenol induced myocardial ischemia.