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心肌细胞短暂低氧可诱导对后续长时间低氧所致细胞严重损伤的耐力增强，已在心脏预处理（PC）模型上得到证实，但PC发生的细胞内信号传导途径目前尚不清楚。我们在培养的新生兔心肌细胞低氧／复氧模型上，观察丝裂素活化蛋白激酶（MAPK）和核蛋白体S6激酶（S6K）活性改变。结果发现：低氧60min后、复氧15min，细胞总MAPK和核MAPK活性分别较对照组增加95％和230％（P＜0．01）；S6K活性在复氧30min轻对照组增高142％（P＜0．01）。应用磷酸酯酶1（Ppase1）抑制剂ocadaicacid（0A，1μmol/L），可加强低氧／复氧引起MAPK和S6K激活，而酪氨酸激酶（TyrK）阻断剂（genistein），蛋白激酶C（PKC）阻断剂（H7）和预先用PKC激动剂（PMA）孵育使细胞PKC下调，都减轻了低氧诱导的MAPK和S6K的激活。蛋白激酶A（PKA）抑制剂（H89）、钙调素依赖蛋白激酶（PKM）抑制剂（W7）和PPase2a抑制剂（0A，10nmol／L）却无影响。结果表明，心肌细胞短暂低氧／复氧激活了MAPK和S6K激活过程为PKC，TyrK和PPasel所参与，似未涉及PKA，PKM和PPase2a。
Short-term myocardial hypoxia can induce prolonged hypoxia-induced cell damage in the endurance enhancement, has been confirmed in the model of cardiac preconditioning (PC), but the PC signal transduction pathway is still not clear. We observed changes of mitogen-activated protein kinase (MAPK) and nucleoprotein S6 kinase (S6K) activity in cultured neonatal rat cardiomyocytes under hypoxia / reoxygenation. The results showed that after 60min of hypoxia, the total MAPK and nuclear MAPK activity increased by 95% and 230%, respectively (P <0.01) after reoxygenation for 15min, while the activity of S6K increased by 142% in reoxygenation 30min light control group P <0.01). Hypoxia / reoxygenation induced activation of MAPK and S6K by application of ocadaicacid (0 A, 1 μmol / L), a Ppase1 inhibitor, while tyrosine kinase (TyrK) genistein, (PKC) blocker (H7) and preincubation with PKC agonist (PMA) downregulated cellular PKC, both attenuated hypoxia-induced MAPK and S6K activation. There was no effect of protein kinase A (PKA) inhibitor (H89), PKM inhibitor (W7) and PPase2a inhibitor (0A, 10nmol / L) The results showed that transient hypoxia / reoxygenation of cardiomyocytes activated MAPK and the activation of S6K was involved in PKC, TyrK and PPasel, but PKA, PKM and PPase2a did not appear to be involved.