各部位心肌细胞对硝酸酯类药物预适应能力的实验研究

目的： 研究各部位的心肌细胞对缺氧再复氧损伤的耐受能力、产生缺氧预适应的能力以及一氧化氮产生预适应保护心肌细胞的途径。 方法： 培养不同部位的心肌细胞（心房、左心室、右心室、心尖和全心脏），分别给予下列的刺激：缺氧复氧，缺氧预适应，低浓度精氨酸预适应，高浓度精氨酸预适应，观察细胞坏死率、细胞凋亡率、培养液中乳酸脱氢酶浓度、细胞内游离钙离子浓度以及细胞内蛋白激酶C的活性强度变化等。 结果： 实验表明，缺氧复氧损伤可以造成不同部位间心肌细胞坏死率和凋亡率明显升高，培养液中LDH的含量增加，细胞内钙离子超载，但各组细胞间并没有明显区别（P>0.05）。给予缺氧预适应后，细胞损伤的各种指标均显著低于缺氧复氧组（P<0.05）。给予细胞不同浓度的精氨酸处理，这些指标同样程度的低于缺氧复氧组（P<0.05），同时细胞内蛋白激酶C的活性高于缺氧复氧组（P<0.05）。 结论： 药物预适应可以对缺氧复氧损伤产生明显的拮抗作用，它可能是通过激活细胞内蛋白激酶C来发挥作用的，而各部位的心肌细胞产生药物预适应的能力没有显著性差别。

Preconditioning effect of nitrate medicine on different parts of the heart and its signaling pathway

AIM: To study the preconditioning effect of nitrate medicine on different parts of the heart and its signaling pathway. METHODS: The cells from different parts of the heart (atrium, left ventricle, right ventricle, apex and the whole heart) were isolated and cultured. The cultured cells were treated with hypoxia and reperfusion, hypoxia preconditioning, 1 mmol/L L-arginine preconditioning and 5 mmol/L L-arginine preconditioning, respectively. The cell necrosis rate, cell apoptosis rate, LDH concentration in the medium, the Ca 2 ]i and PKC activity in the cells were determined. RESULTS: The result show that hypoxia and reperfusion increased the necrosis rate and apoptosis rate, enhanced the concentration of LDH in the medium and the Ca 2 ]i overload in the cells (P<0.05), but there was no difference between these groups (P>0.05). After hypoxia preconditioning and L-arginine preconditioning, these indexes decreased (P<0.05) while the PKC activity increased (P<0.05). CONCLUSION: Nitrate medicine protected the cells from different parts of the heart against hypoxia and reperfusion, and this function may achieve through the activation of PKC.