阿魏酸钠对心肌细胞缺氧/复氧损伤的保护作用及其机制

Protective effect and mechanism of pharmacologic preconditioning induced by sodium ferulate on primary cultured myocardial cell injury by anoxia/reoxygenation

目的 研究阿魏酸钠(SF)预适应对心肌细胞缺氧/复氧损伤的保护作用及其机制。方法 采用1～3d新生SD大鼠,常规方法培养心肌细胞,给予模拟缺氧(缺血)液、模拟复氧(再灌注)液以及药理性预适应药物阿魏酸钠以分析K_(ATP)^+通道、NO及PKC的影响。结果 与对照组比,单纯缺氧/复氧使LDH,CK,MDA及LD水平显著升高,细胞搏动频率、细胞存活率和SOD,GSH-Px活力显著下降。SF预适应后明显减轻上述变化。Glib,L-NAME和Ploy B均部分取消SF预适应的减轻作用。结论 SF预适应对心肌细胞缺氧/复氧损伤有显著的保护作用;此保护心肌过程是多种因素综合作用的结果。

Aim To study the preconditioning effects and mechanism of action of sodium ferulate (SF) on primary cultured myocardial cell injury induced by anoxia/reoxygenation. Methods Cultured myocardial cells of neonatal SD rats were randomly divided into ten groups: control group: without any treatment; anoxia/ reoxygenation group (A/R), reoxygenation of 1 h following anoxia of 3 h; anoxia preconditioning group (AP), reoxygenation of 30 mins following anoxia of 30 mins, three times before the same procedure as group A/R; SF preconditioning groups, 20 rains of SF (1.68, 0.42, 0.105 mmol·L^(-1) in final concentration) preconditioning followed by 10 mins wash out before A/R; K_(ATP)^+ channel blocker group, NOS inhibitor group and PKC inhibitor group, adding gliberclamide, L-NAME, ploymyxin B at final concentration of 12 g·mL^(-1), 50 μmol·L^(-1), 50 μtmol·L^(-1), to culture medium respectively 10 min before the same procedures as SF preconditioning group (1.68 mmol·L^(-1)). Myocardial cells pulse rate and rhythm, myocyte viability, the activity of LDH and CK in culture, the contents of intracelluar MDA, LD in myocardial cells, the activity of SOD and GSH-Px of the cultured myocardial cell were measured at the end of experiment. Results Compared with control group, anoxia/reoxygenation caused great increases of levels of LDH, CK, MDA and LD (P<0.01), decreases of myocardial cells pulse rate, cell viability, SOD and GSH-Px(P<0.01);SF preconditioning significantly attenualed these increases and decreases. Glib, L-NAME, and Ploy B partly abolished the effects of SF preconditioning. Conclusion SF preconditioning is effective in protecting myocardial cells from anoxia injury. The cardioprotective effect of SF preconditioning is produced by multiple factors.