Propranolol reduces anoxia/reoxygenation-mediated injury of adult myocytes through an anti-radical mechanism.
Propranolol reduces anoxia/reoxygenation-mediated injury of adult myocytes through an anti-radical mechanism.
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普萘洛尔通过抗自由基机制减少缺氧/复氧介导的成体肌细胞损伤。
DOI：
10.1016/0022-2828(91)90081-v
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发表时间：
1991
影响因子：
5
通讯作者：
Weglicki,WB
中科院分区：
文献类型：
--
作者：
Kramer,JH;Mak,IT;Freedman,AM;Weglicki,WB
研究了普萘洛尔 (PRO) 和阿替洛尔 (ATE) 对暴露于 30 分钟缺氧（A：95% N 2 5% CO 2）和随后复氧（R：95% O 2 5% CO 2）长达 20 分钟的成年犬肌细胞的影响。在一些研究中，与超氧化物歧化酶（SOD）的效果进行了比较。虽然单独缺氧仅产生最小的损伤，但在缺乏β-阻滞剂或SOD的情况下的再氧合与细胞活力的显着损失、细胞乳酸脱氢酶的释放增加以及脂质过氧化产物的形成增加相关。在 d, 1-PRO (20, 200 μ m) 存在下暴露于 A R 的肌细胞在 20 分钟的复氧过程中得到了实质性的、浓度依赖性的保护。在 2 μm d-PRO（非活性 β 受体阻滞剂）存在的情况下也观察到显着的保护作用，但仅在较长的预孵育期（2 小时）后才发生。 SOD (10 μg/ml) 提供与 200 μm d, 1-PRO 等效的保护。相比之下，水溶性较高的 β 受体阻滞剂 ATE（200 μ m）仅提供轻微的保护。在存在或不存在药物治疗的情况下，还对 A R 肌细胞进行了使用 α-苯基-叔丁基硝酮 (PBN) 的电子自旋共振自旋捕获研究。在 A R 或 SOD 之前短期（10 分钟）暴露于 d, 1-PRO (200 μm)，导致总 PBN 脂质自由基加合物形成减少 71–84%（烷氧基；α H= 2.0− 2.5 G，α N= 13.5− 13.75 G）；长期暴露于 2 μm d-PRO（2 小时）可导致 51% 的减少。这些数据表明，超氧阴离子是导致随后脂质自由基形成的事件的引发剂，并且 PRO 的抗过氧化特性似乎与 β 受体阻断无关。
The effects of propranolol (PRO) and atenolol (ATE) on adult canine myocytes exposed to 30 min anoxia (A: 95% N 2 5% CO 2) and subsequent reoxygenation (R: 95% O 2 5% CO 2) for up to 20 min was investigated. In some studies, comparison of effects were made with that of superoxide dismutase (SOD). Although anoxia alone produced only minimal injury, reoxygenation in the absence of the β-blockers or SOD was associated with significant losses of cellular viability, elevated release of cellular lactate dehydrogenase, and increased formation of lipid peroxidation products. Myocytes exposed to A R in the presence of d, 1-PRO (20, 200 μ m) were afforded substantial, concentration-dependent protection during 20 min reoxygenation. Significant protection was also observed in the presence of 2 μ m d-PRO (non-active β-blocker), but only after a longer preincubation period (2 h). SOD (10 μg/ml) provided equi-potent protection to that of 200 μ m d, 1-PRO. By contrast, the more water-soluble β-blocker, ATE (200 μ m), offered only minor protection. Electron Spin Resonance spin trapping studies using α-phenyl-tert-butylnitrone (PBN) were also performed with A R myocytes in the presence or absence of drug treatment. Short-term (10 min) exposure to d, 1-PRO (200 μ m) prior to A R, or to SOD, resulted in a 71–84% reduction in total PBN lipid radical adduct formation (alkoxyl; α H= 2.0− 2.5 G, α N= 13.5− 13.75 G); long-term exposure (2 h) to 2 μ m d-PRO resulted in a 51% reduction. These data suggest that the superoxide anion was an initiator of events leading to subsequent lipid radical formation and that the anti-peroxidative properties of PRO appear to be independent of β-receptor blockade.