Maulik N, Watanabe M, Engelman D T, Engelman R M, Das D K
Department of Surgery, University of Connecticut School of Medicine, Farmington 06030, USA.
Mol Cell Biochem. 1995 Mar 9;144(1):67-74. doi: 10.1007/BF00926742.
Adaptation to various forms of stress has been found to be associated with increased cellular tolerance to myocardial ischemia. In this study, the effects of myocardial adaptation to oxidative stress was examined by injecting rats with endotoxin (0.5 mg/kg) and its non-toxic derivative, lipid A (0.5 mg/kg). Both compounds exerted oxidative stress within 1 h of treatment as evidenced by enhanced malonaldehyde formation. The oxidative stress disappeared steadily and progressively with time in concert with the appearance of the induction of glutathione and antioxidative enzymes that included superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. After 24 h of endotoxin or lipid A treatment, the amount of oxidative stress and antioxidant enzyme levels were significantly lower and higher, respectively, compared to those at the baseline levels. Corroborating these results, both endotoxin and lipid A provided protection against myocardial ischemia and reperfusion injury as evidenced by a significantly improved postischemic recovery of left ventricular functions. The data presented here demonstrates that a controlled amount of oxidative stress induces the expression of intracellular antioxidants that can result in enhanced myocardial tolerance to ischemia. This suggests that myocardial adaptation to oxidative stress may be a potential tool for reduction of ischemic/reperfusion injury.
研究发现，适应各种形式的应激与细胞对心肌缺血的耐受性增加有关。在本研究中，通过给大鼠注射内毒素（0.5mg/kg）及其无毒衍生物脂多糖（0.5mg/kg），来检测心肌对氧化应激的适应性作用。两种化合物在治疗后1小时内均产生了氧化应激，丙二醛生成增加证明了这一点。随着谷胱甘肽以及包括超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽还原酶在内的抗氧化酶诱导现象的出现，氧化应激随时间稳步且逐渐消失。内毒素或脂多糖治疗24小时后，与基线水平相比，氧化应激量显著降低，抗氧化酶水平显著升高。证实这些结果的是，内毒素和脂多糖均能提供对心肌缺血和再灌注损伤的保护作用，左心室功能缺血后恢复显著改善证明了这一点。此处呈现的数据表明，适量的氧化应激可诱导细胞内抗氧化剂的表达，从而增强心肌对缺血的耐受性。这表明心肌对氧化应激的适应可能是减少缺血/再灌注损伤的一种潜在手段。
