摘要
背景:周期性的环磷酸腺苷浓度改变参与了预适应对缺血心脏的保护作用。目的:观察环磷酸腺苷和一氧化氮在缺氧/复氧心肌细胞后适应保护机制中的可能作用。方法:原代培养SD乳鼠心肌细胞,随机分为11组分别处理:正常对照组、缺氧/复氧组、心肌缺血后适应组、心肌缺血后适应+咯利普兰组、心肌缺血后适应+SQ22536或左旋精氨酸+心肌缺血后适应组,咯利普兰、SQ22536或各浓度Nω-硝基精氨酸+缺氧/复氧组。结果与结论:心肌缺血后适应能显著改善缺氧/复氧损伤造成的心肌细胞活力下降,减少乳酸脱氢酶、肌酸激酶的释放,降低一氧化氮、肿瘤坏死因子α和白细胞介素β的mRNA表达;咯利普兰能进一步增强后适应对心肌细胞的保护作用,而腺苷酸环化酶抑制剂SQ22536可显著减弱该作用;20,100μmol/L非选择性一氧化氮合酶抑制剂Nω-硝基-左旋精氨酸能发挥类似于后适应的保护作用,而在1000μmol/L时则损伤心肌细胞(P<0.05)。证实心肌缺血后适应对缺氧/复氧损伤心肌细胞的保护,可能是通过增强环磷酸腺苷信号抑制炎症过程实现的。
BACKGROUND：Previous studies have shown cyclic increases in tissue cyclic adenosine monophosphate （cAMP） during a multiple-cycle preconditioning protocol and the possibility that cAMP acts as a messenger or signal to elicit protection to subsequent ischemic damage. OBJECTIVE：To investigate the possible effects of cAMP and nitric oxide （NO） in the postconditioning protection of the cardiomyocytes from hypoxia/reoxygenation （H/R） injury. METHODS：Primary cultured Sprague-Dawley neonatal rat cardiomyocytes were randomly divided into 11 groups：normal control, H/R, postconditioning, postconditioning＋rolipram, postconditioning＋SQ22536 or L-arginine＋ postconditioning, rolipram, SQ22536 or Nω-nitro-L-arginine （L-NAME）＋H/R. RESULTS AND CONCLUSION： Ischemic postconditioning significantly improved cell viability, reduced lactate dehydrogenase and creatine kinase release, decreased expression of nitric oxide, tumor necrosis factor-α, and interleukin-β. The specific PDE4 inhibitor rolipram could further strength the protective effect of ischemic postconditioning on cardiomyocytes, while the specific adenylyl cyclase inhibitor SQ22536 could significantly attenuate this effect （P 0.05）. A non-selective nitric oxide synthase inhibitor L-NAME showed the deleterious effect at 1000 μmol/L, while it produced similar effect to ischemic postconditioning at 20 or 100 μmol/L. These findings suggest that the cAMP and NO signaling molecules participate in the protection of postconditioning to cardiomyocytes from H/R injury, and the effect may be associated with regulation of inflammatory process.
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2011年第28期5277-5280,共4页
Journal of Clinical Rehabilitative Tissue Engineering Research
